DB code: S00376

RLCP classification 2.40.18000.65 : Phosphorolysis
CATH domain 3.40.50.1580 : Rossmann fold Catalytic domain
E.C. 2.4.2.28
CSA 1cg6
M-CSA 1cg6
MACiE M0244

CATH domain Related DB codes (homologues)
3.40.50.1580 : Rossmann fold S00510 S00375

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q13126 S-methyl-5''-thioadenosine phosphorylase
EC 2.4.2.28
5''-methylthioadenosine phosphorylase
MTA phosphorylase
MTAPase
NP_002442.2 (Protein)
NM_002451.3 (DNA/RNA sequence)
PF01048 (PNP_UDP_1)
[Graphical View]
P50389 S-methyl-5''-thioadenosine phosphorylase
EC 2.4.2.28
5''-methylthioadenosine phosphorylase
MTA phosphorylase
NP_344028.1 (Protein)
NC_002754.1 (DNA/RNA sequence)
PF01048 (PNP_UDP_1)
[Graphical View]

KEGG enzyme name
S-methyl-5'-thioadenosine phosphorylase
5'-methylthioadenosine nucleosidase
5'-deoxy-5'-methylthioadenosine phosphorylase
MTA phosphorylase
MeSAdo phosphorylase
MeSAdo/Ado phosphorylase
methylthioadenosine phosphorylase
methylthioadenosine nucleoside phosphorylase
5'-methylthioadenosine:phosphate methylthio-D-ribosyl-transferase
S-methyl-5-thioadenosine phosphorylase
S-methyl-5-thioadenosine:phosphateS-methyl-5-thio-alpha-D-ribosyl-transferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q13126 MTAP_HUMAN S-methyl-5''-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate. Homotrimer. Cytoplasm.
P50389 MTAP_SULSO S-methyl-5''-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate. Homohexamer, disulfide-linked.

KEGG Pathways
Map code Pathways E.C.
MAP00271 Methionine metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00170 C00009 C00147 C04188
E.C.
Compound 5'-Methylthioadenosine Orthophosphate Adenine 5-Methylthio-D-ribose 1-phosphate
Type amine group,nucleoside,sulfide group phosphate group/phosphate ion amine group,aromatic ring (with nitrogen atoms) carbohydrate,phosphate group/phosphate ion,sulfide group
ChEBI 17509
 17509
 		26078
 26078
 		16708
 16708
 		27859
 27859
PubChem 439176
 439176
 		1004
 22486802
 1004
 22486802
 		190
 190
 		11988266
 11988266
1cg6A Bound:MTA Analogue:SO4 Unbound Unbound
1cb0A Unbound Unbound Bound:ADE Unbound
1k27A Analogue:MTM Bound:PO4 Unbound Unbound
1jdsA Unbound Bound:PO4 Unbound Unbound
1jdsB Unbound Bound:PO4 Unbound Unbound
1jdsC Unbound Bound:PO4 Unbound Unbound
1jdsD Unbound Bound:PO4 Unbound Unbound
1jdsE Unbound Bound:PO4 Unbound Unbound
1jdsF Unbound Bound:PO4 Unbound Unbound
1jdtA Bound:MTA Analogue:SO4 Unbound Unbound
1jdtB Bound:MTA Analogue:SO4 Unbound Unbound
1jdtC Bound:MTA Analogue:SO4 Unbound Unbound
1jduA Unbound Unbound Unbound Unbound
1jduB Unbound Unbound Unbound Unbound
1jduC Unbound Unbound Unbound Unbound
1jdvA Analogue:ADN Analogue:SO4 Unbound Unbound
1jdvB Analogue:ADN Analogue:SO4 Unbound Unbound
1jdvC Unbound Analogue:SO4 Unbound Unbound
1jdvD Analogue:ADN Analogue:SO4 Unbound Unbound
1jdvE Analogue:ADN Analogue:SO4 Unbound Unbound
1jdvF Unbound Analogue:SO4 Unbound Unbound
1jdzA Analogue:FMB Analogue:SO4 Unbound Unbound
1jdzB Analogue:FMB Analogue:SO4 Unbound Unbound
1jdzC Analogue:FMB Analogue:SO4 Unbound Unbound
1je0A Unbound Bound:PO4 Unbound Unbound
1je0B Unbound Bound:PO4 Unbound Unbound
1je0C Unbound Bound:PO4 Unbound Unbound
1je1A Analogue:GMP Analogue:SO4 Unbound Unbound
1je1B Analogue:GMP Analogue:SO4 Unbound Unbound
1je1C Analogue:GMP Analogue:SO4 Unbound Unbound
1je1D Analogue:GMP Analogue:SO4 Unbound Unbound
1je1E Analogue:GMP Analogue:SO4 Unbound Unbound
1je1F Analogue:GMP Analogue:SO4 Unbound Unbound
1jp7A Unbound Analogue:SO4 Unbound Unbound
1jp7B Unbound Analogue:SO4 Unbound Unbound
1jp7C Unbound Analogue:SO4 Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cg6A ASP 220
1cb0A ASP 220
1k27A ASP 220
1jdsA ASP 205
1jdsB ASP 205
1jdsC ASP 205
1jdsD ASP 205
1jdsE ASP 205
1jdsF ASP 205
1jdtA ASP 205
1jdtB ASP 205
1jdtC ASP 205
1jduA ASP 205
1jduB ASP 205
1jduC ASP 205
1jdvA ASP 205
1jdvB ASP 205
1jdvC ASP 205
1jdvD ASP 205
1jdvE ASP 205
1jdvF ASP 205
1jdzA ASP 205
1jdzB ASP 205
1jdzC ASP 205
1je0A ASP 205
1je0B ASP 205
1je0C ASP 205
1je1A ASP 205
1je1B ASP 205
1je1C ASP 205
1je1D ASP 205
1je1E ASP 205
1je1F ASP 205
1jp7A ASP 205
1jp7B ASP 205
1jp7C ASP 205

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.1380
[2]
Fig.5, p.159-161
[3]
Fig.6, p.636-637
[4]
p.39240-39241
[5]
p.949-950

References
[1]
Resource
Comments
Medline ID
PubMed ID 9351810
Journal Structure
Year 1997
Volume 5
Pages 1373-83
Authors Mao C, Cook WJ, Zhou M, Koszalka GW, Krenitsky TA, Ealick SE
Title The crystal structure of Escherichia coli purine nucleoside phosphorylase: a comparison with the human enzyme reveals a conserved topology.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9746359
Journal Eur J Biochem
Year 1998
Volume 256
Pages 155-62
Authors Allart B, Gatel M, Guillerm D, Guillerm G
Title The catalytic mechanism of adenosylhomocysteine/methylthioadenosine nucleosidase from Escherichia coli--chemical evidence for a transition state with a substantial oxocarbenium character.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 10404592
Journal Structure Fold Des
Year 1999
Volume 7
Pages 629-41
Authors Appleby TC, Erion MD, Ealick SE
Title The structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis.
Related PDB 1cg6 1cb0
Related UniProtKB Q13126
[4]
Resource
Comments
Medline ID
PubMed ID 11489901
Journal J Biol Chem
Year 2001
Volume 276
Pages 39232-42
Authors Appleby TC, Mathews II, Porcelli M, Cacciapuoti G, Ealick SE
Title Three-dimensional structure of a hyperthermophilic 5'-deoxy-5'-methylthioadenosine phosphorylase from Sulfolobus solfataricus.
Related PDB 1jdu 1jdv 1jdt 1jds 1jdz 1je0 1je1 1jp7
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11591349
Journal Structure (Camb)
Year 2001
Volume 9
Pages 941-53
Authors Lee JE, Cornell KA, Riscoe MK, Howell PL
Title Structure of E. coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase reveals similarity to the purine nucleoside phosphorylases.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the PNP phosphorylase family.
The catalysis of this enzyme is generally thought to proceed via a two-step mechanism with formation of an oxocarbenium-like transition state followed by a nucleophilic attack by the phosphate ion at the anomeric carbon in an SN1-like mechanism, according to the literature [5].
Negatively charged residues such as histidine and arginine are involved in phosphate-binding. One of the oxygen atoms of this phosphate ion is in a good position to initially stabilize the partial positive charge on O4' atom of the proposed oxocarbenium ion intermediate [3]. The oxygen atom of the phosphate will make a nucleophilic attack at the anomeric carbon, C1'.
Moreover, a buried aspartic acid residue, Asp220 (PDB; 1cg6), can exhibit a significant increase in pKa, which allows it to be protonated under physiological conditions, according to the paper [3]. If the case is, this aspartic acid residue can protonate N7 of the adenine base, in order to accommodate the flow of negative charge into the base that occurs during the bond cleavage [3].

Created Updated
2002-07-11 2009-02-26