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
26078
16708
27859
PubChem 439176
1004
22486802
190
11988266
1cg6A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:MTA Analogue:SO4 Unbound Unbound
1cb0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADE Unbound
1k27A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:MTM Bound:PO4 Unbound Unbound
1jdsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1jdsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1jdsC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1jdsD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1jdsE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1jdsF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1jdtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:MTA Analogue:SO4 Unbound Unbound
1jdtB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:MTA Analogue:SO4 Unbound Unbound
1jdtC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:MTA Analogue:SO4 Unbound Unbound
1jduA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1jduB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1jduC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1jdvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:ADN Analogue:SO4 Unbound Unbound
1jdvB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:ADN Analogue:SO4 Unbound Unbound
1jdvC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:SO4 Unbound Unbound
1jdvD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:ADN Analogue:SO4 Unbound Unbound
1jdvE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:ADN Analogue:SO4 Unbound Unbound
1jdvF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:SO4 Unbound Unbound
1jdzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:FMB Analogue:SO4 Unbound Unbound
1jdzB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:FMB Analogue:SO4 Unbound Unbound
1jdzC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:FMB Analogue:SO4 Unbound Unbound
1je0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1je0B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1je0C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:PO4 Unbound Unbound
1je1A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:GMP Analogue:SO4 Unbound Unbound
1je1B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:GMP Analogue:SO4 Unbound Unbound
1je1C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:GMP Analogue:SO4 Unbound Unbound
1je1D Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:GMP Analogue:SO4 Unbound Unbound
1je1E Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:GMP Analogue:SO4 Unbound Unbound
1je1F Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:GMP Analogue:SO4 Unbound Unbound
1jp7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:SO4 Unbound Unbound
1jp7B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:SO4 Unbound Unbound
1jp7C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 220
1cb0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 220
1k27A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 220
1jdsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdsC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdsD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdsE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdsF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdtB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdtC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jduA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jduB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jduC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdvB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdvC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdvD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdvE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdvF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdzB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jdzC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je0B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je0C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je1A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je1B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je1C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je1D Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je1E Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1je1F Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jp7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jp7B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 205
1jp7C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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