DB code: D00003

CATH domain 3.40.50.720 : Rossmann fold
3.30.360.10 : Dihydrodipicolinate Reductase; domain 2 Catalytic domain
E.C. 1.1.1.3
CSA 1ebf
M-CSA 1ebf
MACiE

CATH domain Related DB codes (homologues)
3.30.360.10 : Dihydrodipicolinate Reductase; domain 2 T00219 D00010 D00017 D00023 D00027 D00028 D00034 D00476
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00610 S00625 S00319 S00328 S00329 S00330 S00331 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00336 S00334 T00219 S00339 D00513 D00001 D00002 D00005 D00007 D00008 D00010 D00012 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00002 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P31116 Homoserine dehydrogenase
HDH
EC 1.1.1.3
NP_012673.3 (Protein)
NM_001181797.3 (DNA/RNA sequence)
PF00742 (Homoserine_dh)
PF03447 (NAD_binding_3)
[Graphical View]

KEGG enzyme name
homoserine dehydrogenase
HSDH
HSD

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P31116 DHOM_YEAST L-homoserine + NAD(P)(+) = L-aspartate 4- semialdehyde + NAD(P)H. Homodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00260 Glycine, serine and threonine metabolism
MAP00300 Lysine biosynthesis

Compound table
Substrates Products Intermediates
KEGG-id C00263 C00003 C00006 C00441 C00004 C00005 C00080
E.C.
Compound L-Homoserine NAD+ NADP+ L-Aspartate 4-semialdehyde NADH NADPH H+
Type amino acids,carbohydrate amide group,amine group,nucleotide amide group,amine group,nucleotide amino acids,carbohydrate amide group,amine group,nucleotide amide group,amine group,nucleotide others
ChEBI 15699
 57476
 15699
 57476
 		15846
 15846
 		18009
 18009
 		18051
 537519
 18051
 537519
 		16908
 16908
 		16474
 16474
 		15378
 15378
PubChem 12647
 6971022
 12647
 6971022
 		5893
 5893
 		5886
 5886
 		439235
 5287708
 439235
 5287708
 		439153
 439153
 		5884
 5884
 		1038
 1038
1ebfA01 Unbound Bound:NAD Unbound Unbound Unbound Unbound
1ebfB01 Unbound Unbound Unbound Unbound Unbound Unbound
1ebuA01 Unbound Unbound Unbound Unbound Unbound Unbound
1ebuB01 Unbound Unbound Unbound Unbound Unbound Unbound
1ebuC01 Unbound Unbound Unbound Unbound Unbound Unbound
1ebuD01 Unbound Analogue:NDA Unbound Unbound Unbound Unbound
1q7gA01 Unbound Analogue:NHO Unbound Unbound Unbound Unbound
1q7gB01 Unbound Unbound Unbound Unbound Unbound Unbound
1tveA01 Unbound Unbound Unbound Unbound Unbound Unbound
1tveB01 Unbound Unbound Unbound Unbound Unbound Unbound
1ebfA02 Unbound Unbound Unbound Unbound Unbound Unbound
1ebfB02 Unbound Unbound Unbound Unbound Unbound Unbound
1ebuA02 Unbound Unbound Unbound Unbound Unbound Unbound
1ebuB02 Unbound Unbound Unbound Unbound Unbound Unbound
1ebuC02 Unbound Unbound Unbound Unbound Unbound Unbound
1ebuD02 Bound:HSE Unbound Unbound Unbound Unbound Unbound
1q7gA02 Unbound Unbound Unbound Unbound Unbound Unbound
1q7gB02 Unbound Unbound Unbound Unbound Unbound Unbound
1tveA02 Unbound Unbound Unbound Unbound Unbound Unbound
1tveB02 Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ebfA01
1ebfB01
1ebuA01
1ebuB01
1ebuC01
1ebuD01
1q7gA01
1q7gB01
1tveA01
1tveB01
1ebfA02 ASP 219;LYS 223
1ebfB02 ASP 219;LYS 223
1ebuA02 ASP 219;LYS 223
1ebuB02 ASP 219;LYS 223
1ebuC02 ASP 219;LYS 223
1ebuD02 ASP 219;LYS 223
1q7gA02 ASP 219;LYS 223
1q7gB02 ASP 219;LYS 223
1tveA02 ASP 219;LYS 223
1tveB02 ASP 219;LYS 223

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[12]
Fig.5a, p.242-243
[13]
Scheme 1, Scheme 2, p.51-53

References
[1]
Resource
Comments
Medline ID
PubMed ID 4388077
Journal Biochim Biophys Acta
Year 1969
Volume 171
Pages 205-16
Authors Bryan JK
Title Studies on the catalytic and regulatory properties of homoserine dehydrogenase of Zea mays roots.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 4397398
Journal Biochim Biophys Acta
Year 1971
Volume 235
Pages 1-13
Authors Bothwell MA, Datta P
Title Effects of K+ on the catalytic and regulatory properties of homoserine dehydrogenase of Pseudomonas fluorescens.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 4562990
Journal Eur J Biochem
Year 1972
Volume 28
Pages 520-7
Authors Veron M, Falcoz-Kelly F, Cohen GN
Title The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12. The two catalytic activities are carried by two independent regions of the polypeptide chain.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 4149354
Journal Eur J Biochem
Year 1973
Volume 38
Pages 325-35
Authors Veron M, Saari JC, Villar-Palasi C, Cohen GN
Title The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K 12. Intra and intersubunit interactions between the catalytic regions of the bifunctional enzyme.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 182215
Journal Biochemistry
Year 1976
Volume 15
Pages 3704-10
Authors Wright JK, Feldman J, Takahashi M
Title Cobalt(III) affinity-labeled aspartokinase. Formation of substrate and inhibitor adducts.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 414912
Journal Eur J Biochem
Year 1978
Volume 82
Pages 453-61
Authors Epstein CC, Datta P
Title Homoserine dehydrogenase of Rhodospirillum rubrum. Physical and chemical characterization.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 6774337
Journal Proc Natl Acad Sci U S A
Year 1980
Volume 77
Pages 3379-83
Authors Garel JR, Dautry-Varsat A
Title Sequential folding of a bifunctional allosteric protein.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 6365907
Journal J Biol Chem
Year 1984
Volume 259
Pages 2252-6
Authors Muller K, Garel JR
Title The interaction between Escherichia coli aspartokinase-homoserine dehydrogenase and 3-acetylpyridine-adenine dinucleotide phosphate (reduced), an analog of NADPH.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 2241177
Journal Arch Biochem Biophys
Year 1990
Volume 283
Pages 96-101
Authors Angeles TS, Viola RE
Title The kinetic mechanisms of the bifunctional enzyme aspartokinase-homoserine dehydrogenase I from Escherichia coli.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8432719
Journal J Bacteriol
Year 1993
Volume 175
Pages 959-65
Authors Omori K, Komatsubara S
Title Role of serine 352 in the allosteric response of Serratia marcescens aspartokinase I-homoserine dehydrogenase I analyzed by using site-directed mutagenesis.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 9761913
Journal Acta Crystallogr D Biol Crystallogr
Year 1998
Volume 54
Pages 413-5
Authors DeLaBarre B, Jacques SL, Pratt CE, Ruth DA, Wright GD, Berghuis AM
Title Crystallization and preliminary X-ray diffraction studies of homoserine dehydrogenase from Saccharomyces cerevisiae.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10700284
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 238-44
Authors DeLaBarre B, Thompson PR, Wright GD, Berghuis AM
Title Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases.
Related PDB 1ebf 1ebu
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11341915
Journal Biochim Biophys Acta
Year 2001
Volume 1544
Pages 42-54
Authors Jacques SL, Ejim LJ, Wright GD
Title Homoserine dehydrogenase from Saccharomyces cerevisiae: kinetic mechanism and stereochemistry of hydride transfer.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11341914
Journal Biochim Biophys Acta
Year 2001
Volume 1544
Pages 28-41
Authors Jacques SL, Nieman C, Bareich D, Broadhead G, Kinach R, Honek JF, Wright GD
Title Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11888289
Journal Biochemistry
Year 2002
Volume 41
Pages 3720-5
Authors James CL, Viola RE
Title Production and characterization of bifunctional enzymes. Domain swapping to produce new bifunctional enzymes in the aspartate pathway.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 14583265
Journal Chem Biol
Year 2003
Volume 10
Pages 989-95
Authors Jacques SL, Mirza IA, Ejim L, Koteva K, Hughes DW, Green K, Kinach R, Honek JF, Lai HK, Berghuis AM, Wright GD
Title Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase.
Related PDB 1q7g
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 15210149
Journal Bioorg Med Chem
Year 2004
Volume 12
Pages 3825-30
Authors Ejim L, Mirza IA, Capone C, Nazi I, Jenkins S, Chee GL, Berghuis AM, Wright GD
Title New phenolic inhibitors of yeast homoserine dehydrogenase.
Related PDB 1tve
Related UniProtKB

Comments

Created Updated
2004-03-24 2009-02-26