DB code: D00085

RLCP classification 6.30.264850.5200 : Double-bonded atom exchange
3.748.90280.5472 : Transfer
5.12.1504210.1 : Elimination
4.202.3822800.1 : Addition
8.11211.913550.5730 : Isomerization
6.40.528600.5540 : Double-bonded atom exchange
CATH domain 3.40.640.10 : Aspartate Aminotransferase; domain 2 Catalytic domain
3.90.1150.10 : Aspartate Aminotransferase, domain 1
E.C. 2.1.2.1
CSA 1dfo
M-CSA 1dfo
MACiE M0147

CATH domain Related DB codes (homologues)
3.40.640.10 : Aspartate Aminotransferase; domain 2 D00092 D00101 D00102 D00103 D00104 D00107 D00108 D00109 D00255 D00257 D00258 D00265 D00269 D00515 M00031 D00279
3.90.1150.10 : Aspartate Aminotransferase, domain 1 D00092 D00101 D00102 D00103 D00104 D00107 D00108 D00109 D00255 D00257 D00258 D00265 D00269 D00515 M00031 D00279

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0A825 Serine hydroxymethyltransferase
SHMT
Serine methylase
EC 2.1.2.1
NP_417046.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_490779.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF00464 (SHMT)
[Graphical View]
Q5SI56 Serine hydroxymethyltransferase
SHMT
Serine methylase
EC 2.1.2.1
YP_144790.1 (Protein)
NC_006461.1 (DNA/RNA sequence)
PF00464 (SHMT)
[Graphical View]
Q7SIB6 Serine hydroxymethyltransferase
SHMT
Serine methylase
EC 2.1.2.1
PF00464 (SHMT)
[Graphical View]
P50431 Serine hydroxymethyltransferase, cytosolic
SHMT
EC 2.1.2.1
Glycine hydroxymethyltransferase
Serine methylase
NP_033197.2 (Protein)
NM_009171.2 (DNA/RNA sequence)
PF00464 (SHMT)
[Graphical View]
P07511 Serine hydroxymethyltransferase, cytosolic
SHMT
EC 2.1.2.1
Glycine hydroxymethyltransferase
Serine methylase
NP_001095187.1 (Protein)
NM_001101717.1 (DNA/RNA sequence)
PF00464 (SHMT)
[Graphical View]
P34896 Serine hydroxymethyltransferase, cytosolic
SHMT
EC 2.1.2.1
Glycine hydroxymethyltransferase
Serine methylase
NP_004160.3 (Protein)
NM_004169.3 (DNA/RNA sequence)
NP_683718.1 (Protein)
NM_148918.1 (DNA/RNA sequence)
PF00464 (SHMT)
[Graphical View]
P34897 Serine hydroxymethyltransferase, mitochondrial
SHMT
EC 2.1.2.1
Glycine hydroxymethyltransferase
Serine methylase
NP_001159828.1 (Protein)
NM_001166356.1 (DNA/RNA sequence)
NP_001159829.1 (Protein)
NM_001166357.1 (DNA/RNA sequence)
NP_001159830.1 (Protein)
NM_001166358.1 (DNA/RNA sequence)
NP_001159831.1 (Protein)
NM_001166359.1 (DNA/RNA sequence)
NP_005403.2 (Protein)
NM_005412.5 (DNA/RNA sequence)
PF00464 (SHMT)
[Graphical View]

KEGG enzyme name
glycine hydroxymethyltransferase
serine aldolase
threonine aldolase
serine hydroxymethylase
serine hydroxymethyltransferase
allothreonine aldolase
L-serine hydroxymethyltransferase
L-threonine aldolase
serine hydroxymethyltransferase
serine transhydroxymethylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0A825 GLYA_ECOLI 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. Homotetramer. Cytoplasm. Pyridoxal phosphate.
Q5SI56 GLYA_THET8 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. Homotetramer (By similarity). Cytoplasm (By similarity). Pyridoxal phosphate (By similarity).
Q7SIB6 Q7SIB6_BACST 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. Pyridoxal phosphate. Pyridoxal phosphate (By similarity).
P50431 GLYC_MOUSE 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. Homotetramer. Cytoplasm. Pyridoxal phosphate (By similarity).
P07511 GLYC_RABIT 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. Homotetramer. Cytoplasm. Pyridoxal phosphate.
P34896 GLYC_HUMAN 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. Homotetramer. Cytoplasm. Pyridoxal phosphate.
P34897 GLYM_HUMAN 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. Homotetramer. Mitochondrion. Pyridoxal phosphate.

KEGG Pathways
Map code Pathways E.C.
MAP00260 Glycine, serine and threonine metabolism
MAP00460 Cyanoamino acid metabolism
MAP00670 One carbon pool by folate
MAP00680 Methane metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00018 C00065 C00101 C00037 C00143 C00001 I00043 C00067 I00045 I00046 I00047 I00044 I00048
E.C.
Compound Pyridoxal phosphate L-Serine Tetrahydrofolate Glycine 5,10-Methylenetetrahydrofolate H2O External aldimine intermediate (PLP-L-Ser) Formaldehyde Quinonoid intermediate (PLP-Gly) 5-hydroxymethylene-tetrahydrofolate 5-iminium-tetrahydrofolate External aldimine intermediate (PLP-Gly) Gem-diamine transition-state (active-site-Lys-PLP-Gly)
Type aromatic ring (with nitrogen atoms),phosphate group/phosphate ion amino acids,carbohydrate amino acids,amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carboxyl group amino acids amino acids,amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carboxyl group H2O
ChEBI 18405
 18405
 		17115
 33384
 17115
 33384
 		15635
 20506
 15635
 20506
 		15428
 57305
 15428
 57305
 		15377
 15377
PubChem 1051
 1051
 		5951
 6857581
 5951
 6857581
 		5460413
 91443
 5460413
 91443
 		5257127
 750
 5257127
 750
 		439175
 439175
 		22247451
 962
 22247451
 962
1dfoA01 Analogue:PLG Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FFO Intermediate-bound:PLG Unbound
1dfoB01 Analogue:PLG Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FFO Intermediate-bound:PLG Unbound
1dfoC01 Analogue:PLG Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FFO Intermediate-bound:PLG Unbound
1dfoD01 Analogue:PLG Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FFO Intermediate-bound:PLG Unbound
1eqbA01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FFO Intermediate-bound:GLY-PLP Unbound
1eqbB01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FFO Intermediate-bound:GLY-PLP Unbound
1eqbC01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FFO Intermediate-bound:GLY-PLP Unbound
1eqbD01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FFO Intermediate-bound:GLY-PLP Unbound
2dkjA01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dkjB01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kkjA02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kkpA02 Bound:PLP Unbound Unbound Unbound Unbound Intermediate-bound:SER-PLP Unbound Unbound Unbound Unbound
1kl1A02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:GLY-PLP Unbound
1kl2A02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FON Intermediate-bound:GLY-PLP Unbound
1kl2B02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:FON Intermediate-bound:GLY-PLP Unbound
1yjsA02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:GLY-PLP Unbound
1yjyA02 Bound:PLP Unbound Unbound Unbound Unbound Intermediate-bound:SER-PLP Unbound Unbound Unbound Unbound
1yjzA02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2vgtA01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:GLY-PLP Unbound
2vguA01 Bound:PLP Unbound Unbound Unbound Unbound Intermediate-bound:SER-PLP Unbound Unbound Unbound Unbound
2vgvA01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:GLY-PLP Unbound
2vgwA01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-bound:GLY-PLP-LYS_226
2vi9A01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:GLY-PLP Unbound
2viaA01 Bound:PLP Unbound Unbound Unbound Unbound Intermediate-bound:SER-PLP Unbound Unbound Unbound Unbound
2vibA01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:GLY-PLP Unbound
1ejiA02 Analogue:PLG Unbound Unbound Unbound Unbound Unbound Intermediate-bound:PLG Intermediate-bound:THF Unbound Unbound
1ejiB02 Analogue:PLG Unbound Unbound Unbound Unbound Unbound Intermediate-bound:PLG Intermediate-bound:THF Unbound Unbound
1ejiC02 Analogue:PLG Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-bound:PLG-LYS_257
1ejiD02 Analogue:PLG Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:THF Unbound Transition-state-bound:PLG-LYS_257
1cj0A02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cj0B02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ls3A02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-bound:GLY-PLP-LYS_229
1ls3B02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:TGF Unbound Unbound
1ls3C02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-bound:GLY-PLP-LYS_229
1ls3D02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:TGF Unbound Unbound
1rv3A02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rv3B02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-bound:GLY-PLP-LYS_257
1rv4A02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rv4B02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rvuA02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rvuB02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rvyA02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-bound:PLG-LYS_257
1rvyB02 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bj4A01 Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2a7vA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dfoA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dfoB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dfoC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dfoD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eqbA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eqbB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eqbC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eqbD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dkjA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dkjB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kkjA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kkpA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kl1A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kl2A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kl2B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1yjsA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1yjyA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1yjzA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2vgtA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2vguA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2vgvA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2vgwA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2vi9A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2viaA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2vibA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ejiA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ejiB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ejiC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ejiD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cj0A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cj0B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ls3A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ls3B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ls3C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ls3D01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rv3A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rv3B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rv4A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rv4B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rvuA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rvuB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rvyA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1rvyB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bj4A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2a7vA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature[26], [30], [31], [38], [41], [46], [48]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dfoA01 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1dfoB01 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1dfoC01 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1dfoD01 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1eqbA01 GLU 57; ;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding) mutant Y65F
1eqbB01 GLU 57; ;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding) mutant Y65F
1eqbC01 GLU 57; ;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding) mutant Y65F
1eqbD01 GLU 57; ;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding) mutant Y65F
2dkjA01 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding)
2dkjB01 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding)
1kkjA02 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding)
1kkpA02 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding)
1kl1A02 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding)
1kl2A02 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding)
1kl2B02 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding)
1yjsA02 GLU 53;TYR 61;ASP 197;THR 223; mutant K226Q
1yjyA02 GLU 53;TYR 61;ASP 197;THR 223; mutant K226M
1yjzA02 GLU 53;TYR 61;ASP 197;THR 223; mutant K226M
2vgtA01 ;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding) mutant E53Q
2vguA01 ;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding) mutant E53Q
2vgvA01 ;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding) mutant E53Q
2vgwA01 ;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding) mutant E53Q
2vi9A01 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding) mutant S172A
2viaA01 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding) mutant S172A
2vibA01 GLU 53;TYR 61;ASP 197;THR 223;LYS 226 LYS 226(Pyridoxal phosphate binding) mutant S172A
1ejiA02 GLU 75;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding)
1ejiB02 GLU 75;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding)
1ejiC02 GLU 75;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding)
1ejiD02 GLU 75;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding)
1cj0A02 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1cj0B02 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1ls3A02 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1ls3B02 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1ls3C02 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1ls3D02 GLU 57;TYR 65;ASP 200;THR 226;LYS 229 LYS 229(Pyridoxal phosphate binding)
1rv3A02 ;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding) mutant E75L
1rv3B02 ;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding) mutant E75L
1rv4A02 ;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding) mutant E75L
1rv4B02 ;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding) mutant E75L
1rvuA02 ;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding) mutant E75Q
1rvuB02 ;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding) mutant E75Q
1rvyA02 ;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding) mutant E75Q
1rvyB02 ;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding) mutant E75Q
1bj4A01 GLU 75;TYR 83;ASP 228;THR 254;LYS 257 LYS 257(Pyridoxal phosphate binding)
2a7vA01 GLU 82; ;ASP 235;THR 261;LYS 264 LYS 264(Pyridoxal phosphate binding) invisible 84-95, 148-178
1dfoA02
1dfoB02
1dfoC02
1dfoD02
1eqbA02
1eqbB02
1eqbC02
1eqbD02
2dkjA02
2dkjB02
1kkjA01
1kkpA01
1kl1A01
1kl2A01
1kl2B01
1yjsA01
1yjyA01
1yjzA01
2vgtA02
2vguA02
2vgvA02
2vgwA02
2vi9A02
2viaA02
2vibA02
1ejiA01
1ejiB01
1ejiC01
1ejiD01
1cj0A01
1cj0B01
1ls3A01
1ls3B01
1ls3C01
1ls3D01
1rv3A01
1rv3B01
1rv4A01
1rv4B01
1rvuA01
1rvuB01
1rvyA01
1rvyB01
1bj4A02
2a7vA02

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[17]
Fig.6, p.24360-24361
[22]
Figure 1, p.1105, p.1110-1113
[25]
Scheme 1, p.8352-8357
[26]
Fig.17, Fig.18, p.394-397
[28]
Scheme 1, p.7499
[29]
Fig.1, p.13320-13223
[30]
Scheme 1, p.5974-5975
[31]
Fig.4, p.1443-1446
[33]
p.411-413
[34]
Scheme 1, p.156-157, p.162-166
[36]
Scheme 1
[38]
Scheme I, Scheme II, p.17168
[41]
Fig.1, p.24-25, p.27-28
[47]
Fig.1, p.6865-6867
[49]
Scheme 1, p.6930, p.6935-6936
[50]
p.4154-4155

References
[1]
Resource
Comments
Medline ID
PubMed ID 3536510
Journal Eur J Biochem
Year 1986
Volume 161
Pages 45-9
Authors Schirch V, Schirch D, Martini F, Bossa F
Title Serine hydroxymethyltransferase. Effect of proteases on the activity and structure of the cytosolic enzyme.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1849406
Journal Biochem J
Year 1991
Volume 274
Pages 807-12
Authors Malthouse JP, Milne JJ, Gariani LS
Title A comparative study of the kinetics and stereochemistry of the serine hydroxymethyltransferase- and tryptophan synthase-catalysed exchange of the pro-2R and pro-2S protons of glycine.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1765122
Journal Experientia
Year 1991
Volume 47
Pages 1104-18
Authors Smith DM, Thomas NR, Gani D
Title A comparison of pyridoxal 5'-phosphate dependent decarboxylase and transaminase enzymes at a molecular level.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1536856
Journal Biochemistry
Year 1992
Volume 31
Pages 2155-64
Authors Stover P, Schirch V
Title Enzymatic mechanism for the hydrolysis of 5,10-methenyltetrahydropteroylglutamate to 5-formyltetrahydropteroylglutamate by serine hydroxymethyltransferase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1577761
Journal J Biol Chem
Year 1992
Volume 267
Pages 9289-93
Authors Usha R, Savithri HS, Rao NA
Title Arginine residues involved in binding of tetrahydrofolate to sheep liver serine hydroxymethyltransferase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8405393
Journal FEBS Lett
Year 1993
Volume 331
Pages 145-9
Authors Pascarella S, Schirch V, Bossa F
Title Similarity between serine hydroxymethyltransferase and other pyridoxal phosphate-dependent enzymes.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8226831
Journal J Biol Chem
Year 1993
Volume 268
Pages 23132-8
Authors Schirch D, Delle Fratte S, Iurescia S, Angelaccio S, Contestabile R, Bossa F, Schirch V
Title Function of the active-site lysine in Escherichia coli serine hydroxymethyltransferase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8478924
Journal J Mol Biol
Year 1993
Volume 230
Pages 1094-6
Authors Stover P, Kruschwitz H, Schirch V, Wright HT
Title Diffraction grade crystals of Escherichia coli serine hydroxymethyltransferase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7947980
Journal Biochim Biophys Acta
Year 1994
Volume 1209
Pages 40-50
Authors Bhaskar B, Prakash V, Savithri HS, Rao NA
Title Interactions of L-serine at the active site of serine hydroxymethyltransferases: induction of thermal stability.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8003988
Journal Protein Sci
Year 1994
Volume 3
Pages 701-5
Authors Pascarella S, Bossa F
Title Similarity between pyridoxal/pyridoxamine phosphate-dependent enzymes involved in dideoxy and deoxyaminosugar biosynthesis and other pyridoxal phosphate enzymes.
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Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8674620
Journal Biochem Soc Trans
Year 1996
Volume 24
Pages 132S
Authors Fitzpatrick TB, Malthouse JP
Title Proof that serine hydroxymethyltransferase retains its specificity for the pro-2S proton of glycine in the absence of tetrahydrofolate.
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[12]
Resource
Comments
Medline ID
PubMed ID 8910307
Journal J Biol Chem
Year 1996
Volume 271
Pages 27311-20
Authors Cai K, Schirch V
Title Structural studies on folding intermediates of serine hydroxymethyltransferase using fluorescence resonance energy transfer.
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[13]
Resource
Comments
Medline ID
PubMed ID 8621691
Journal J Biol Chem
Year 1996
Volume 271
Pages 2987-94
Authors Cai K, Schirch V
Title Structural studies on folding intermediates of serine hydroxymethyltransferase using single tryptophan mutants.
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[14]
Resource
Comments
Medline ID
PubMed ID 8860659
Journal Protein Expr Purif
Year 1996
Volume 7
Pages 323-8
Authors Iurescia S, Condo I, Angelaccio S, Delle Fratte S, Bossa F
Title Site-directed mutagenesis techniques in the study of Escherichia coli serine hydroxymethyltransferase.
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[15]
Resource
Comments
Medline ID
PubMed ID 9584848
Journal Acta Biochim Pol
Year 1997
Volume 44
Pages 679-88
Authors Talwar R, Jagath JR, Datta A, Prakash V, Savithri HS, Rao NA
Title The role of lysine-256 in the structure and function of sheep liver recombinant serine hydroxymethyltransferase.
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[16]
Resource
Comments
Medline ID
PubMed ID 9398220
Journal Biochemistry
Year 1997
Volume 36
Pages 14956-64
Authors Kastanos EK, Woldman YY, Appling DR
Title Role of mitochondrial and cytoplasmic serine hydroxymethyltransferase isozymes in de novo purine synthesis in Saccharomyces cerevisiae.
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[17]
Resource
Comments
Medline ID
PubMed ID 9305893
Journal J Biol Chem
Year 1997
Volume 272
Pages 24355-62
Authors Jagath JR, Sharma B, Rao NA, Savithri HS
Title The role of His-134, -147, and -150 residues in subunit assembly, cofactor binding, and catalysis of sheep liver cytosolic serine hydroxymethyltransferase.
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[18]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9757129
Journal Acta Crystallogr D Biol Crystallogr
Year 1998
Volume 54
Pages 1030-1
Authors Renwick SB, Skelly JV, Chave KJ, Sanders PG, Snell K, Baumann U
Title Purification, crystallization and preliminary X-ray analysis of human recombinant cytosolic serine hydroxymethyltransferase.
Related PDB 1bj4
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9523719
Journal Eur J Biochem
Year 1998
Volume 252
Pages 113-7
Authors Fitzpatrick TB, Malthouse JP
Title A substrate-induced change in the stereospecificity of the serine-hydroxymethyltransferase-catalysed exchange of the alpha-protons of amino acids--evidence for a second catalytic site.
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[20]
Resource
Comments
Medline ID
PubMed ID 9843671
Journal J Struct Biol
Year 1998
Volume 123
Pages 169-74
Authors Kazanina G, Radaev S, Wright HT, Schirch V
Title Crystal forms and subunit stoichiometry of serine hydroxymethyltransferase.
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[21]
Resource
Comments
Medline ID
PubMed ID 9761478
Journal Protein Sci
Year 1998
Volume 7
Pages 1976-82
Authors Pascarella S, Angelaccio S, Contestabile R, Delle Fratte S, Di Salvo M, Bossa F
Title The structure of serine hydroxymethyltransferase as modeled by homology and validated by site-directed mutagenesis.
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[22]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 11-480
Medline ID 98428667
PubMed ID 9753690
Journal Structure
Year 1998
Volume 6
Pages 1105-16
Authors Renwick SB, Snell K, Baumann U
Title The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy.
Related PDB
Related UniProtKB P34896
[23]
Resource
Comments
Medline ID
PubMed ID 10600164
Journal Arch Biochem Biophys
Year 1999
Volume 372
Pages 271-9
Authors di Salvo ML, Delle Fratte S, Maras B, Bossa F, Wright HT, Schirch V
Title Deamidation of asparagine residues in a recombinant serine hydroxymethyltransferase.
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[24]
Resource
Comments
Medline ID
PubMed ID 10493937
Journal Biochem J
Year 1999
Volume 343 Pt 1
Pages 257-63
Authors Krishna Rao JV, Jagath JR, Sharma B, Appaji Rao N, Savithri HS
Title Asp-89: a critical residue in maintaining the oligomeric structure of sheep liver cytosolic serine hydroxymethyltransferase.
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[25]
Resource
Comments
Medline ID
PubMed ID 10387080
Journal Biochemistry
Year 1999
Volume 38
Pages 8347-58
Authors Scarsdale JN, Kazanina G, Radaev S, Schirch V, Wright HT
Title Crystal structure of rabbit cytosolic serine hydroxymethyltransferase at 2.8 A resolution: mechanistic implications.
Related PDB 1cj0
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[26]
Resource
Comments
Medline ID
PubMed ID 10828359
Journal Adv Enzyme Regul
Year 2000
Volume 40
Pages 353-403
Authors Snell K, Baumann U, Byrne PC, Chave KJ, Renwick SB, Sanders PG, Whitehouse SK
Title The genetic organization and protein crystallographic structure of human serine hydroxymethyltransferase.
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[27]
Resource
Comments
Medline ID
PubMed ID 10970801
Journal Biochem J
Year 2000
Volume 350 Pt 3
Pages 849-53
Authors Talwar R, Leelavathy V, Krishna Rao JV, Appaji Rao N, Savithri HS
Title Role of pro-297 in the catalytic mechanism of sheep liver serine hydroxymethyltransferase.
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[28]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10858298
Journal Biochemistry
Year 2000
Volume 39
Pages 7492-500
Authors Contestabile R, Angelaccio S, Bossa F, Wright HT, Scarsdale N, Kazanina G, Schirch V
Title Role of tyrosine 65 in the mechanism of serine hydroxymethyltransferase.
Related PDB 1eqb
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[29]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11063567
Journal Biochemistry
Year 2000
Volume 39
Pages 13313-23
Authors Szebenyi DM, Liu X, Kriksunov IA, Stover PJ, Thiel DJ
Title Structure of a murine cytoplasmic serine hydroxymethyltransferase quinonoid ternary complex: evidence for asymmetric obligate dimers.
Related PDB 1eji
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[30]
Resource
Comments
Medline ID
PubMed ID 10998057
Journal Eur J Biochem
Year 2000
Volume 267
Pages 5967-76
Authors Rao JV, Prakash V, Rao NA, Savithri HS
Title The role of Glu74 and Tyr82 in the reaction catalyzed by sheep liver cytosolic serine hydroxymethyltransferase.
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[31]
Resource
Comments
Medline ID
PubMed ID 10691982
Journal Eur J Biochem
Year 2000
Volume 267
Pages 1441-6
Authors Talwar R, Jagath JR, Rao NA, Savithri HS
Title His230 of serine hydroxymethyltransferase facilitates the proton abstraction step in catalysis.
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[32]
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Comments
Medline ID
PubMed ID 10716626
Journal Int J Biochem Cell Biol
Year 2000
Volume 32
Pages 289-301
Authors Ogawa H, Gomi T, Fujioka M
Title Serine hydroxymethyltransferase and threonine aldolase: are they identical?
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[33]
Resource
Comments
Medline ID
PubMed ID 10762066
Journal Int J Biochem Cell Biol
Year 2000
Volume 32
Pages 405-16
Authors Rao NA, Talwar R, Savithri HS
Title Molecular organization, catalytic mechanism and function of serine hydroxymethyltransferase--a potential target for cancer chemotherapy.
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[34]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS)
Medline ID 20124005
PubMed ID 10656824
Journal J Mol Biol
Year 2000
Volume 296
Pages 155-68
Authors Scarsdale JN, Radaev S, Kazanina G, Schirch V, Wright HT
Title Crystal structure at 2.4 A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate.
Related PDB 1dfo
Related UniProtKB P0A825
[35]
Resource
Comments
Medline ID
PubMed ID 11305908
Journal Biochemistry
Year 2001
Volume 40
Pages 4932-9
Authors Liu X, Szebenyi DM, Anguera MC, Thiel DJ, Stover PJ
Title Lack of catalytic activity of a murine mRNA cytoplasmic serine hydroxymethyltransferase splice variant: evidence against alternative splicing as a regulatory mechanism.
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[36]
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Comments
Medline ID
PubMed ID 11737206
Journal Eur J Biochem
Year 2001
Volume 268
Pages 6508-25
Authors Contestabile R, Paiardini A, Pascarella S, di Salvo ML, D'Aguanno S, Bossa F
Title l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions.
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[37]
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Medline ID
PubMed ID 12356312
Journal Biochemistry
Year 2002
Volume 41
Pages 12115-23
Authors Bhatt AN, Prakash K, Subramanya HS, Bhakuni V
Title Different unfolding pathways for mesophilic and thermophilic homologues of serine hydroxymethyltransferase.
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[38]
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Medline ID
PubMed ID 11877399
Journal J Biol Chem
Year 2002
Volume 277
Pages 17161-9
Authors Trivedi V, Gupta A, Jala VR, Saravanan P, Rao GS, Rao NA, Savithri HS, Subramanya HS
Title Crystal structure of binary and ternary complexes of serine hydroxymethyltransferase from Bacillus stearothermophilus: insights into the catalytic mechanism.
Related PDB 1kkj 1kkp 1kl1 1kl2
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[39]
Resource
Comments
Medline ID
PubMed ID 12089472
Journal J Biosci
Year 2002
Volume 27
Pages 233-42
Authors Jala VR, Prakash V, Rao NA, Savithri HS
Title Overexpression and characterization of dimeric and tetrameric forms of recombinant serine hydroxymethyltransferase from Bacillus stearothermophilus.
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[40]
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Comments
Medline ID
PubMed ID 12392447
Journal Biochem J
Year 2003
Volume 369
Pages 469-76
Authors Jala VR, Appaji Rao N, Savithri HS
Title Identification of amino acid residues, essential for maintaining the tetrameric structure of sheep liver cytosolic serine hydroxymethyltransferase, by targeted mutagenesis.
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[41]
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Medline ID
PubMed ID 12686103
Journal Biochim Biophys Acta
Year 2003
Volume 1647
Pages 24-9
Authors Appaji Rao N, Ambili M, Jala VR, Subramanya HS, Savithri HS
Title Structure-function relationship in serine hydroxymethyltransferase.
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[42]
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Medline ID
PubMed ID 12686123
Journal Biochim Biophys Acta
Year 2003
Volume 1647
Pages 138-42
Authors Malthouse JP
Title Stereospecificity of alpha-proton exchange reactions catalysed by pyridoxal-5'-phosphate-dependent enzymes.
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[43]
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Medline ID
PubMed ID 12902326
Journal J Biol Chem
Year 2003
Volume 278
Pages 41789-97
Authors Angelaccio S, Chiaraluce R, Consalvi V, Buchenau B, Giangiacomo L, Bossa F, Contestabile R
Title Catalytic and thermodynamic properties of tetrahydromethanopterin-dependent serine hydroxymethyltransferase from Methanococcus jannaschii.
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[44]
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Medline ID
PubMed ID 12773539
Journal J Biol Chem
Year 2003
Volume 278
Pages 31088-94
Authors Fu TF, Boja ES, Safo MK, Schirch V
Title Role of proline residues in the folding of serine hydroxymethyltransferase.
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[45]
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Medline ID
PubMed ID 12514178
Journal J Biol Chem
Year 2003
Volume 278
Pages 10142-9
Authors Zanetti KA, Stover PJ
Title Pyridoxal phosphate inhibits dynamic subunit interchange among serine hydroxymethyltransferase tetramers.
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[46]
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Comments
Medline ID
PubMed ID 12438316
Journal J Biol Chem
Year 2003
Volume 278
Pages 2645-53
Authors Fu TF, Scarsdale JN, Kazanina G, Schirch V, Wright HT
Title Location of the pteroylpolyglutamate-binding site on rabbit cytosolic serine hydroxymethyltransferase.
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[47]
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Comments
Medline ID
PubMed ID 15170323
Journal Biochemistry
Year 2004
Volume 43
Pages 6865-76
Authors Szebenyi DM, Musayev FN, di Salvo ML, Safo MK, Schirch V
Title Serine hydroxymethyltransferase: role of glu75 and evidence that serine is cleaved by a retroaldol mechanism.
Related PDB 1rv3 1rv4 1rvu 1rvy
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[48]
Resource
Comments
Medline ID
PubMed ID 15273312
Journal Protein Sci
Year 2004
Volume 13
Pages 2184-95
Authors Bhatt AN, Khan MY, Bhakuni V
Title The C-terminal domain of dimeric serine hydroxymethyltransferase plays a key role in stabilization of the quaternary structure and cooperative unfolding of protein: domain swapping studies with enzymes having high sequence identity.
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[49]
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Comments
Medline ID
PubMed ID 15865438
Journal Biochemistry
Year 2005
Volume 44
Pages 6929-37
Authors Bhavani S, Trivedi V, Jala VR, Subramanya HS, Kaul P, Prakash V, Appaji Rao N, Savithri HS
Title Role of Lys-226 in the catalytic mechanism of Bacillus stearothermophilus serine hydroxymethyltransferase--crystal structure and kinetic studies.
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[50]
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Comments
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PubMed ID 17651438
Journal FEBS J
Year 2007
Volume 274
Pages 4148-60
Authors Rajaram V, Bhavani BS, Kaul P, Prakash V, Appaji Rao N, Savithri HS, Murthy MR
Title Structure determination and biochemical studies on Bacillus stearothermophilus E53Q serine hydroxymethyltransferase and its complexes provide insights on function and enzyme memory.
Related PDB 2vgt 2vgu 2vgv 2vgw
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Comments
This enzyme belongs to the type-I PLP-dependent enzyme superfamily (Aspartate aminotransferase superfamily, AAT; D00101 in EzCatDB).
There have been several possible catalytic mechanisms proposed for this enzyme (see [47]). Among these mechanisms, including the retro-aldol cleavage reaction (see [34], [38]) and the nucleophilic direct displacement reaction (see [38]), the concerted mechanism that combines the retro-aldol cleavage and the nucleophilic direct displacement reaction seems most likely (see [47], [50]).
This catalytic mechanism is composed of the following reactions:
(A) Formation of external aldimine (with amine group of L-Serine): Exchange of double-bonded atoms.
(B) SN1-like transfer of hydroxymethyl group from Ser-PLP to N5 of tetrahydrofolate (THF), forming a quinonoid intermediate of PLP-Gly (I00045) and a carbinolamine intermediate of THF (I00046).
(C) Elimination of hydroxyl group from the carbinolamine intermediate, forming an iminium cation intermediate of THF (I00047).
(D) Intramolecular addition of N10 to the carbon atom of the iminium cation.
(E or D') Isomerization (change in the position of double-bond), forming an external aldimine (Gly-PLP) from the quinonoid intermediate.
(F) Formation of internal aldimine, leading to the elimination of the product (Gly) from PLP: Exchange of double-bonded atoms.
These reactions proceed as follows:
(A) Formation of external aldimine (with amine group of L-Serine): Exchange of double-bonded atoms.
(A1) The negatively charged O3 atom of PLP modulates the pKa of the alpha-amino group of substrate, L-serine (Ser), and also the pKa of the internal aldimine with Lys229 (of 1dfo). Here, according to the literature from D00101 (D00101 [46], [59] & [61]), the imine-pyridine torsion (or strain) of PLP-Schiff base lowers pKa of the internal aldimine, without lowering pKa of the external aldimine. In any case, the difference in the pKa values facilitates the proton transfer from the alpha-amino group of Ser to the NZ nitrogen of Lys229. Moreover, the alpha-carboxylate of Ser may deprotonate the nucleophile, the alpha-amino group of Ser (see D00106 [10]).
(A2) The deprotonated amine group of Ser makes a nucleophilic attack on the C4' carbon of PLP, forming a transient geminal diamine intermediate.
(A3) There must be a general base, which deprotonates the amine group of the previously Ser substrate, so that the lone pair of the amine group can attack on the C4' atom to form a double-bond, and to release the amine of the catalytic residue, Lys229. Considering the active-site structure, Tyr55' (from the adjacent chain) may play the role as the general base, although the literature has not mentioned it (except for the literature from D00101 [11]). (The released Lys229 must be deprotonated, so that it can act as a general base at the final stage.) However, according to the active site structure of geminal diamine intermediate, the short distance between the NZ atom of Lys229 and amine group of the amino acid substrate suggests that a direct proton transfer can occur. Moreover, according to the literature [34], Thr226 stabilizes the unprotonated NZ atom of Lys229 (acting as a modulator).
(A4) The lone pair of the amine group (of Ser) makes a nucleophilic attack on the C4' atom to form a double-bond, releasing the amine of Lys229, leading to the formation of the external aldimine with L-Ser.
(B) Transfer of hydroxymethyl group from Ser-PLP to N5 of tetrahydrofolate (THF), forming a quinonoid intermediate of PLP-Gly (I00045) and a carbinolamine intermediate of THF (I00046).
(B1) Asp200 interacts with the N1 atom of PLP, modulating and enhancing the activity of the PLP cofactor as an electron sink, leading to polarization of the C2-C3 (or alpha-beta carbon atoms) bond, with positive charge accumulating on the C3 atom (see [47]; D00101 [17], [24]). The hydrogen-bond from Glu57 to O-gamma increases the charge on the C3 even further (Glu57 acting as a modulator?). Thus, the polarized C2-C3 bond is easily broken (see [47]).
(B2) A general base deprotonates the N5 atom of THF for its activation. (A water can be the weak base.)
(B3) The activated N5 atom makes a nucleophilic attack on the beta-carbon (or C3) atom of Ser-PLP, cleaving the C2-C3 bond to give a carbinolamine intermediate (I00046; THF-CH2OH) and a quinonoid intermediate of Gly-PLP (I00045). Asp200 may stabilize the quinonoid intermediate, through the interaction with the N1 atom of PLP (see D00271 [8]). This transfer reaction is an SN2-like reaction (see [47]).
(C) Elimination of hydroxyl group from the carbinolamine intermediate, forming an iminium cation intermediate of THF (I00047).
(C1) Glu57 acts as a general acid to protonate the hydroxyl group of the carbinolamine intermediate.
(C2) The hydroxyl group is eliminated from the intermediate to form a water molecule, forming a 5-iminium-THF (I00047).
(D) Intramolecular addition of N10 to the carbon atom of the iminium cation.
(D1) Glu57 acts as a general base to deprotonate the N10 atom (added group) of the iminium cation intermediate.
(D2) The activated the N10 atom makes a nucleophilic attack on the carbon atom of the iminium cation (addition site), forming a covalent bond with it.
(E or D') Isomerization (change in the position of double-bond), forming an external aldimine (Gly-PLP) from the quinonoid intermediate.
(E1) Although Tyr65' stabilizes the quinonoid intermediate (see [30]), it may act as a general acid to protonate the C2 atom of the quinonoid intermediate.
(E2) This reaction produces an external aldimine intermediate (I00044; Gly-PLP).
(F) Formation of internal aldimine, leading to the elimination of the product (Gly) from PLP: Exchange of double-bonded atoms.
(F1) Thr226 stabilizes the unprotonated NZ atom of Lys229 (acting as a modulator).
(F2) The deprotonated amine group of Lys229 makes a nucleophilic attack on the C4' carbon of the PLP of the external aldimine, forming a transient geminal diamine intermediate.
(F3) The lone pair of the amine nitrogen of Lys229 can attack on the C4' atom to form a double-bond, and to release the amine of the second product, Gly.
(F4) The negatively charged O3 atom of PLP modulates the pKa of the alpha-amino group of product, Gly, and also the pKa of the internal aldimine with Lys229. In any case, the difference in the pKa values facilitates the proton transfer from the NZ nitrogen of Lys229 to the alpha-amine group of Gly. The alpha-carboxylate of Gly may protonate the leaving group, the alpha-amino group of Gly (see D00106 [10]).

Created Updated
2004-11-25 2009-02-26