EzCatDB: S00376

DB codeS00376
RLCP classification2.40.18000.65
CATH domainDomain 13.40.50.1580Catalytic domain
E.C.2.4.2.28
CSA1cg6
MACiEM0244

CATH domainRelated DB codes (homologues)
3.40.50.1580S00510,S00375

Enzyme Name
Swiss-protKEGG

Q13126P50389
Protein nameS-methyl-5''-thioadenosine phosphorylaseS-methyl-5''-thioadenosine phosphorylaseS-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
SynonymsEC 2.4.2.28
5''-methylthioadenosine phosphorylase
MTA phosphorylase
MTAPase
EC 2.4.2.28
5''-methylthioadenosine phosphorylase
MTA phosphorylase

KEGG pathways
MAP codePathways
MAP00271Methionine metabolism

Swiss-prot:Accession NumberQ13126P50389
Entry nameMTAP_HUMANMTAP_SULSO
ActivityS-methyl-5''-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate.S-methyl-5''-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate.
SubunitHomotrimer.Homohexamer, disulfide-linked.
Subcellular locationCytoplasm.
Cofactor



SubstratesProducts
KEGG-idC00170C00009C00147C04188
Compound5'-MethylthioadenosineOrthophosphateAdenine5-Methylthio-D-ribose 1-phosphate
Typeamine group,nucleoside,sulfide groupphosphate group/phosphate ionamine group,aromatic ring (with nitrogen atoms)carbohydrate,phosphate group/phosphate ion,sulfide group
1cg6ABound:MTAAnalogue:SO4UnboundUnbound
1cb0AUnboundUnboundBound:ADEUnbound
1k27AAnalogue:MTMBound:PO4UnboundUnbound
1jdsAUnboundBound:PO4UnboundUnbound
1jdsBUnboundBound:PO4UnboundUnbound
1jdsCUnboundBound:PO4UnboundUnbound
1jdsDUnboundBound:PO4UnboundUnbound
1jdsEUnboundBound:PO4UnboundUnbound
1jdsFUnboundBound:PO4UnboundUnbound
1jdtABound:MTAAnalogue:SO4UnboundUnbound
1jdtBBound:MTAAnalogue:SO4UnboundUnbound
1jdtCBound:MTAAnalogue:SO4UnboundUnbound
1jduAUnboundUnboundUnboundUnbound
1jduBUnboundUnboundUnboundUnbound
1jduCUnboundUnboundUnboundUnbound
1jdvAAnalogue:ADNAnalogue:SO4UnboundUnbound
1jdvBAnalogue:ADNAnalogue:SO4UnboundUnbound
1jdvCUnboundAnalogue:SO4UnboundUnbound
1jdvDAnalogue:ADNAnalogue:SO4UnboundUnbound
1jdvEAnalogue:ADNAnalogue:SO4UnboundUnbound
1jdvFUnboundAnalogue:SO4UnboundUnbound
1jdzAAnalogue:FMBAnalogue:SO4UnboundUnbound
1jdzBAnalogue:FMBAnalogue:SO4UnboundUnbound
1jdzCAnalogue:FMBAnalogue:SO4UnboundUnbound
1je0AUnboundBound:PO4UnboundUnbound
1je0BUnboundBound:PO4UnboundUnbound
1je0CUnboundBound:PO4UnboundUnbound
1je1AAnalogue:GMPAnalogue:SO4UnboundUnbound
1je1BAnalogue:GMPAnalogue:SO4UnboundUnbound
1je1CAnalogue:GMPAnalogue:SO4UnboundUnbound
1je1DAnalogue:GMPAnalogue:SO4UnboundUnbound
1je1EAnalogue:GMPAnalogue:SO4UnboundUnbound
1je1FAnalogue:GMPAnalogue:SO4UnboundUnbound
1jp7AUnboundAnalogue:SO4UnboundUnbound
1jp7BUnboundAnalogue:SO4UnboundUnbound
1jp7CUnboundAnalogue:SO4UnboundUnbound

Active-site residues
pdbCatalytic residues
1cg6AASP 220
1cb0AASP 220
1k27AASP 220
1jdsAASP 205
1jdsBASP 205
1jdsCASP 205
1jdsDASP 205
1jdsEASP 205
1jdsFASP 205
1jdtAASP 205
1jdtBASP 205
1jdtCASP 205
1jduAASP 205
1jduBASP 205
1jduCASP 205
1jdvAASP 205
1jdvBASP 205
1jdvCASP 205
1jdvDASP 205
1jdvEASP 205
1jdvFASP 205
1jdzAASP 205
1jdzBASP 205
1jdzCASP 205
1je0AASP 205
1je0BASP 205
1je0CASP 205
1je1AASP 205
1je1BASP 205
1je1CASP 205
1je1DASP 205
1je1EASP 205
1je1FASP 205
1jp7AASP 205
1jp7BASP 205
1jp7CASP 205

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID9351810
JournalStructure
Year1997
Volume5
Pages1373-83
AuthorsMao C, Cook WJ, Zhou M, Koszalka GW, Krenitsky TA, Ealick SE
TitleThe crystal structure of Escherichia coli purine nucleoside phosphorylase: a comparison with the human enzyme reveals a conserved topology.
[2]
PubMed ID9746359
JournalEur J Biochem
Year1998
Volume256
Pages155-62
AuthorsAllart B, Gatel M, Guillerm D, Guillerm G
TitleThe catalytic mechanism of adenosylhomocysteine/methylthioadenosine nucleosidase from Escherichia coli--chemical evidence for a transition state with a substantial oxocarbenium character.
[3]
PubMed ID10404592
JournalStructure Fold Des
Year1999
Volume7
Pages629-41
AuthorsAppleby TC, Erion MD, Ealick SE
TitleThe structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis.
Related PDB1cg6,1cb0
Related Swiss-protQ13126
[4]
PubMed ID11489901
JournalJ Biol Chem
Year2001
Volume276
Pages39232-42
AuthorsAppleby TC, Mathews II, Porcelli M, Cacciapuoti G, Ealick SE
TitleThree-dimensional structure of a hyperthermophilic 5'-deoxy-5'-methylthioadenosine phosphorylase from Sulfolobus solfataricus.
Related PDB1jdu,1jdv,1jdt,1jds,1jdz,1je0,1je1,1jp7
[5]
PubMed ID11591349
JournalStructure (Camb)
Year2001
Volume9
Pages941-53
AuthorsLee JE, Cornell KA, Riscoe MK, Howell PL
TitleStructure of E. coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase reveals similarity to the purine nucleoside phosphorylases.

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].

createdupdated
2002-07-112009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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