Information on EC 2.4.2.28 - S-methyl-5'-thioadenosine phosphorylase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
2.4.2.28
-
RECOMMENDED NAME
GeneOntology No.
S-methyl-5'-thioadenosine phosphorylase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
sequential mechanism
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
sequential mechanism
Caldariella acidophila
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
catalytic mechanism
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
catalytic mechanism
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
active and substrate-binding sites, three-dimensional structures
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
active and substrate-binding sites, three-dimensional structures
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
phosphorolytic mechanism
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
phosphorolytic mechanism
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
phosphorolytic mechanism
Caldariella acidophila
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
ordered bisubstrate biproduct reaction with methylthioadenosine the first substrate to add and adenine the last product to leave the enzyme
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
equilibrium-ordered reaction, 5'-methylthioadenosine is the first substrate to bind and 5-methylthioribose 1-phosphate is the first product to be released
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
subunit structure, model
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
3 binding sites between substrate and enzyme
-
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
transition state structure, computational modeling of the transition state, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pentosyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Cysteine and methionine metabolism
-
-
Metabolic pathways
-
-
polyamine pathway
-
-
S-methyl-5'-thioadenosine degradation II
-
-
SYSTEMATIC NAME
IUBMB Comments
S-methyl-5'-thioadenosine:phosphate S-methyl-5-thio-alpha-D-ribosyl-transferase
Also acts on 5'-deoxyadenosine and other analogues having 5'-deoxy groups.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5'-deoxy-5'-methylthioadenosine phosphorylase
-
-
-
-
5'-deoxy-5'-methylthioadenosine phosphorylase
-
-
5'-deoxy-5'-methylthioadenosine phosphorylase
Q8U4Q8
-
5'-deoxy-5'-methylthioadenosine phosphorylase
P50389
-
5'-deoxy-5'-methylthioadenosine phosphorylase II
-
-
5'-deoxy-5'-methylthioadenosine phosphorylase II
Q97W94
-
5'-deoxy-5'-methylthioadenosine phosphorylase II
Q97W94
-
-
5'-deoxy-5'-methylthioadenosine:orthophosphate methylthioribosyltransferase
-
-
5'-deoxy-5'-methylthioadenosine:orthophosphate methylthioribosyltransferase
Q9CQ65
-
5'-methylthioadenosine nucleosidase
-
-
-
-
5'-methylthioadenosine nucleosidase
Q7XA67
-
5'-methylthioadenosine nucleosidase
Q9T0I8
-
5'-methylthioadenosine nucleosidase
-
-
5'-methylthioadenosine nucleosidase
Escherichia coli O157:H7 EDL933
-
-
-
5'-methylthioadenosine nucleosidase
-
-
5'-methylthioadenosine phosphorylase
-
-
-
-
5'-methylthioadenosine phosphorylase
-
-
5'-methylthioadenosine phosphorylase
Q9CQ65
-
5'-methylthioadenosine phosphorylase
-
-
5'-methylthioadenosine phosphorylase
P50389
-
5-methylthioadenosine phosphorylase
-
-
5-methylthioadenosine phosphorylase
-
-
5-methylthioadenosine phosphorylase
P50389
-
MeSAdo phosphorylase
-
-
-
-
MeSAdo/Ado phosphorylase
-
-
-
-
methylthioadenosine nucleosidase
-
-
methylthioadenosine nucleoside phosphorylase
-
-
-
-
methylthioadenosine phosphorylase
-
-
-
-
methylthioadenosine phosphorylase
-
-
methylthioadenosine phosphorylase
Q13126
-
methylthioadenosine phosphorylase
-
-
methylthioadenosine phosphorylase
-
-
MTA phosphorylase
-
-
-
-
MTA phosphorylase
-
-
MTA phosphorylase
-
-
MTAN
Escherichia coli O157:H7 EDL933
-
-
-
MTAP
Q13126
-
MTAP
-
-
MTAP
Q9CQ65
-
MTAP
Q97W94
-
-
Mtap protein
-
-
MTAPase
-
-
-
-
PfMTAP
Q8U4Q8
-
phosphorylase, methylthioadenosine
-
-
-
-
Rv0535
O06401
gene name
SsMTAP II
Q97W94
-
SsMTAP II
Q97W94
-
-
SsMTAPII
Q97W94
-
SSO2343
Q97W94
locus name
SSO2343
Q97W94
locus name
-
CAS REGISTRY NUMBER
COMMENTARY
61970-06-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Caldariella acidophila
-
-
-
Manually annotated by BRENDA team
O157:H7 EDL933
-
-
Manually annotated by BRENDA team
Escherichia coli O157:H7 EDL933
O157:H7 EDL933
-
-
Manually annotated by BRENDA team
recombinant
UniProt
Manually annotated by BRENDA team
telomeric methylthioadenosine phosphorylase gene MTAP
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
Wistar
-
-
Manually annotated by BRENDA team
strains BB170 and BB120
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
mice homozygous for a MTAP null allele (MtaplacZ) have an embryonic lethal phenotype dying around day 8 postconception. Mtap/MtaplacZ heterozygotes are born at Mendelian frequencies and appear indistinguishable from wild-type mice during the first year of life, but tend to die prematurely with a median survival of 585 days. These animals have greatly enlarged spleens, altered thymic histology, and lymphocytic infiltration of their livers, consistent with lymphoma
malfunction
-
none of MTAN deletion mutants interact with calcineurin B-like 3
physiological function
-
MTAN is involved in pollen development
physiological function
-
Mtap is essential during embryogenesis. Mtap is a tumor suppressor gene independent of CDKN2A and ARF
physiological function
-
MTAP substrates protect MTAP-positive cells from toxicity of adenine analogs 2,6-diaminopurine, 6-methylpurine, and 2-fluoroadenine and clinical cancer drugs 5-fluorouracil or 6-thioguanine. Adenine analog plus 5'-methylthioadenosine, kills MTAP-negative A549 lung tumor cells, while MTAP-positive human fibroblasts are protected, whereas in co-cultures of the breast tumor cell line, MCF-7, and HF cells, MCF-7 is inhibited or killed, while HF cells proliferate robustly
physiological function
-
role of MTAN in quorum sensing
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2',3'-dideoxyadenosine + phosphate
adenine + 2,3-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
substrate for trypanosomal but not for mammalian enzyme
-
-
?
2'-deoxy-2'-amino-5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 2-deoxy-2-amino-5-thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxy-2'-azido-5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 2-deoxy-2-azido-5-thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxy-2-fluoro-5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 2-deoxy-2-fluoro-5-thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxy-5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 2-deoxy-5-thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxyadenosine + phosphate
adenine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxyadenosine + phosphate
adenine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
low activity
-
-
r
2'-deoxyadenosine + phosphate
adenine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
substrate for trypanosomal but not for mammalian enzyme
-
-
?
2-amino-5'-deoxy-5'-(hydroxyethylthio)adenosine + phosphate
2-aminoadenosine + 5-hydroxyethylthio-D-ribose 1-phosphate
show the reaction diagram
-
28% activity compared to 5'-methyladenosine or 5'-deoxy-5'-(hydroxyethylthio)adenosine
-
-
?
2-chloro-2'-deoxyadenosine + phosphate
2-chloroadenine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
2-chloro-5'-O-methyl-2'-deoxyadenosine + phosphate
2-chloroadenine + 5-O-methyl-2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
2-chloroadenosine + phosphate
2-chloroadenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
2-fluoro-5'-deoxy-5'-(hydroxyethylthio)adenosine + phosphate
2-fluoroadenosine + 5-hydroxyethylthio-D-ribose 1-phosphate
show the reaction diagram
-
149% activity compared to 5'-methyladenosine or 5'-deoxy-5'-(hydroxyethylthio)adenosine
-
-
?
3'-deoxy-5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 3-deoxy-5-thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
3'-deoxyadenosine + phosphate
adenine + 3-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
substrate for trypanosomal but not for mammalian enzyme
-
-
?
5'-butylthioadenosine + phosphate
adenine + 5-butylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
24% relative activity
-
-
?
5'-butylthioadenosine + phosphate
adenine + 5-butylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
25% relative activity
-
-
?
5'-chloroadenosine + phosphate
adenine + 5-deoxy-5-chloro-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
13% relative activity
-
-
?
5'-chloroadenosine + phosphate
adenine + 5-deoxy-5-chloro-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
4% relative activity
-
-
?
5'-deoxy-5'-(1,3-thiazol)-2-yl-sulfanyladenosine + phosphate
adenine + 5-(1,3-thiazol-2-yl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(2-(pyridin-2-yl)ethyl)-thioadenosine + phosphate
adenine + 5-ethylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(2-methylbutyl)-thioadenosine + phosphate
adenine + 5-(2-methylbutyl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(2-methylphenyl)-thioadenosine + phosphate
adenine + 5-(2-methylphenyl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(3-methylphenyl)-thioadenosine + phosphate
adenine + 5-(3-methylphenyl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(4-methoxyphenyl)-thioadenosine + phosphate
adenine + 5-(4-methoxyphenyl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(4-methylphenyl)-thioadenosine + phosphate
adenine + 5-(4-methylphenyl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(hydroxyethylthio)adenosine + phosphate
adenine + 5-hydroxyethylthio-D-ribose 1-phosphate
show the reaction diagram
-
trypanocidal substrate analogue
-
-
?
5'-deoxy-5'-(hydroxyethylthio)adenosine + phosphate
adenine + 5-hydroxyethylthio-D-ribose 1-phosphate
show the reaction diagram
-
preincubation of cells with the substrate lead to 22-37% inhibition of spermidine synthesis from ornithine and 2-7fold increased cytosolic levels of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine, and up to 8fold increased cytosolic level of 5'-methyladenosine
-
-
-
5'-deoxy-5'-(phenylethyl)-thioadenosine + phosphate
adenine + 5-phenylethylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(phenylmethyl)-thioadenosine + phosphate
adenine + 5-phenylmethylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-(quinolin-2-yl)-sulfanyladenosine + phosphate
adenine + 5-(quinolin-2-yl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-butylthioadenosine + phosphate
adenine + 5-butylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-cyclohexyl-thioadenosine + phosphate
adenine + 5-cyclohexylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-cyclopentyl-thioadenosine + phosphate
adenine + 5-cyclopentylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-ethylthioadenosine + phosphate
adenine + 5-ethylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-hydroxyethylthioadenosine + phosphate
adenine + 5-(2-hydroxyethyl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-imidazol-2-yl-sulfanyladenosine + phosphate
adenine + 5-(imidazol-2-yl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-isobutylthioadenosine + phosphate
adenine + 5-isobutylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-isopentylthioadenosine + phosphate
adenine + 5-isopentylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-methyl-thioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Q13126
-
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
substrate-induced conformational change involving Glu163, which is located at the interface between subunits and swings in toward the active site upon nucleoside binding
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
sugar specificity
-
r
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
the transition state is stabilized in different ways for 6-amino versus 6-oxo substrates
-
-
?
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
salvage reaction
-
-
-
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
involved in cardiac purine breakdown during ischemia
-
-
-
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
substrate is a by-product of polyamine biosynthesis, which is essential for cell growth and proliferation
-
-
-
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
5'-deoxy-5'-phenyl-thioadenosine + phosphate
adenine + 5-phenylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-phenylmethylene-adenosine + phosphate
adenine + 5-deoxy-5-phenylmethylene-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-pyridin-2-yl-sulfanyladenosine + phosphate
adenine + 5-(pyridin-2-yl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-pyridin-4-yl-sulfanyladenosine + phosphate
adenine + 5-(pyridin-4-yl)thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-tert-butylthioadenosine + phosphate
adenine + 5-tert-butylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-[4-(trifluoromethyl)phenyl]-thioadenosine + phosphate
adenine + 5-[4-(trifluoromethyl)phenyl]thio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'phenylaminoadenosine + phosphate
adenine + 5-deoxy-5-phenylamino-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-adenosine + phosphate
adenine + 5-thio-D-ribose 1 phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxyadenosine + phosphate
adenine + 5-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxyadenosine + phosphate
adenine + 5-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
5'-deoxyadenosine + phosphate
adenine + 5-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxyadenosine + phosphate
adenine + 5-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
phosphate-dependent
-
r
5'-ethylthioadenosine + phosphate
adenine + 5-ethylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-ethylthioadenosine + phosphate
adenine + 5-ethylthio-D-ribose 1-phosphate
show the reaction diagram
-
60% of the activity with 5'-methylthioadenosine
-
-
?
5'-ethylthioadenosine + phosphate
adenine + 5-ethylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
40% relative activity
-
-
?
5'-ethylthioadenosine + phosphate
adenine + 5-ethylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
42% relative activity
-
-
?
5'-iodo-5'-deoxyadenosine + phosphate
adenine + 5-iodo-5-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
5'-iodoadenosine + phosphate
adenine + 5-deoxy-5-iodo-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
17% relative activity
-
-
?
5'-iodoadenosine + phosphate
adenine + 5-deoxy-5-iodo-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
28% relative activity
-
-
?
5'-isobutylthioadenosine + phosphate
adenine + 5-isobutylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
97% of the reaction with 5'-methylthioadenosine
-
-
?
5'-isobutylthioadenosine + phosphate
adenine + 5-isobutylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
32% relative activity
-
-
?
5'-isobutylthioadenosine + phosphate
adenine + 5-isobutylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
17% relative activity
-
-
?
5'-isobutylthioinosine + phosphate
hypoxanthine + 5-isobutylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
8.1% of the reaction with 5'-methylthioadenosine
-
-
?
5'-methylselenoadenosine + phosphate
adenine + 5-methylseleno-D-ribose 1-phosphate
show the reaction diagram
-
95% of the activity with 5'-methylthioadenosine
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Q13126
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Q13126
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Q9CQ65
-
-
-
r
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
100% relative activity
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
5'-methylthioadenosine is the best substrate
-
-
r
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
binding of phosphate and 5-methylthioribose 1-phosphate to the enzyme induces a conformational transition that stabilizes the folded structure of the enzyme
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
preferred direction of reaction is temperature-dependent
-
-
r
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
5'-methylthioadenosine and adenine form ternary complexes with the enzyme only in presence of phosphate and methylthioribose 1-phosphate, respectively
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
completely dependent on phosphate
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
completely dependent on phosphate
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
completely dependent on phosphate
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
important for the salvage of adenine and methionine
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
an antiproliferative effect on stimulated human lymphocytes and virally transformed mouse fibroblasts
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
involved in salvage of adenine and methionine from 5'-methylthioadenosine
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
involved in salvage of adenine and methionine from 5'-methylthioadenosine
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
physiological significance of 5'-methylthioadenosine cleavage is probably related to removal of the thioether which in turn exerts a significant inhibition on methyl transfer reactions
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
the enzyme regulates ornithine decarboxylase by production of downstream metabolites. Tumor suppressor activity of MTAP may be due to its effect on ornithine decarboxylase activity
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
structural comparison of MTA phosphorylase and MTA/AdoHcy nucleosidase explains substrate preferences and identifies regions exploitable for inhibitor design
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
adenine-bound MTAN1 is exclusively in its closed form, substantial conformational changes occur in this region during the enzymatic reaction. Residues Met35, Val90, Leu181, Met201, Phe237 and Ile143', Ile145' and Phe148' in a neighboring MTAN1 monomer bind adenine via hydrophobic and van der Waals interactions. The hydrophobic side chains Phe237 and Leu181 show structural perturbations that provide the flexible accommodation of the adenine ring. The carboxylic side chain of Asp225 hydrogen bonds with nitrogen atoms in the adenine ring, therefore being key determinant for the adenine base. The side chain Thr116 and backbone Gly118 also interact with the adenine molecule, hydrolysis of 5'-methylthioadenosine predominates despite MTAN2 possessing both 5'-methylthioadenosine and S-adenosylhomocysteine hydrolysis activity. MTAN2 binds 5'-methylthioadenosine approximately 6fold higher than S-adenosylhomocysteine. Residues between 216 and 225 in MTAN2 contain conformational differences representing an open conformation when compared with MTAN1. The side chains Met22, Val78, Met168, Met188, Phe224 along with Ile130', Val132' and Leu135' in a neighboring MTAN2 monomer bind adenine via hydrophobic and van der Waals interactions. The hydrophobic side chains Phe224 and Met168 show structural perturbations that provide the flexible accommodation of the adenine ring. The carboxylic side chain of Asp211 hydrogen bonds with nitrogen atoms in the adenine ring, therefore being key determinant for the adenine base. The side chain Thr103 and backbone Gly105 also interact with the adenine molecule
-
-
?
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
the [3'-2H] kinetic isotope effect is consistent with a unique H3'-endo-exo configuration and 3'-hydroxyl polarization without full ionization at the MTAN transition state. The MTAN transition state is a fully dissociative (SN1), ribooxacarbenium-like structure with its C1'-N9 distance larger than 3.2 A. The ribosyl moiety adopts a H3'-endo-exo transition conformation, and the 3'-OH residue is partially polarized by the adjacent carboxylate with a hydrogen bond distance of 2.83 A. The MTAN transition state has a geometry between the unrestrained H3'-endo 5'-methylthioadenosine substrate and a fully developed 3'-exo ribooxacarbenium ion
-
-
ir
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Escherichia coli O157:H7 EDL933
-
-
-
-
?
5'-methylthioadenosine + phosphate
adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
O06401
-
-
-
?
5'-methylthioinosine + phosphate
hypoxanthine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
-
-
-
?
5'-methylthioinosine + phosphate
hypoxanthine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
8.9% of the reaction with 5'-methylthioadenosine
-
-
?
5'-methylthioinosine + phosphate
hypoxanthine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
8.8% of the reaction with 5'-methylthioadenosine
-
-
?
5'-n-butylthioadenosine + phosphate
adenine + 5-n-butylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
93.3% of the reaction with 5'-methylthioadenosine
-
-
?
5'-n-propylthioadenosine + phosphate
adenine + 5-n-propylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-phenyladenosine + phosphate
adenine + 5-phenyl-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-phenylthioadenosine + phosphate
adenine + 5-phenylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
39% relative activity
-
-
?
5'-phenylthioadenosine + phosphate
adenine + 5-phenylthio-D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
12% relative activity
-
-
?
6-methylpurine 2'-deoxyribonucleoside + phosphate
6-methylpurine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
substrate for trypanosomal but not for mammalian enzyme
-
-
?
9-[2-deoxy-beta-D-ribofuranosyl]-6-methylpurine + phosphate
?
show the reaction diagram
-
a toxic prodrug, 5% of the activity with S-methyl-5'-thioadenosine
-
-
?
9-[6-deoxy-beta-L-talofuranosyl]-2-F-adenine + phosphate
?
show the reaction diagram
-
a toxic prodrug, 23% of the activity with S-methyl-5'-thioadenosine
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
Q7XA67, Q9T0I8
6% relative activity
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
O06401
2.1% activity compared to activity with 5'-methylthioadenosine
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
guanosine + phosphate
guanine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
guanosine + phosphate
guanine + D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
?
guanosine + phosphate
guanine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
inosine + phosphate
hypoxanthine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
inosine + phosphate
hypoxanthine + D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
-
inosine + phosphate
hypoxanthine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-homocysteine + phosphate
?
show the reaction diagram
O06401
0.81% activity compared to activity with 5'-methylthioadenosine
-
-
?
S-adenosylhomocysteine + ?
?
show the reaction diagram
-
-
-
-
?
S-adenosylhomocysteine + phosphate
?
show the reaction diagram
Q7XA67, Q9T0I8
14% relative activity
-
-
?
S-methyl-5'-thioadenosine + arsenate
adenine + S-methyl-5-thio-alpha-D-ribose 1-arsenate
show the reaction diagram
-
arsenolysis
-
-
?
S-methyl-5'-thioadenosine + phosphate
adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
S-methyl-5'-thioadenosine + phosphate
adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
S-methyl-5'-thioadenosine + phosphate
adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
-
phosphorolysis
-
-
?
S-methyl-5'-thioadenosine + phosphate
adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
-
recycling of 5'-methylthioadenosine, the byproduct from spermine and spermidine synthesis, to S-adenosylmethionine, the precursor for polyamine synthesis, pathway overview
-
-
?
inosine + phosphate
hypoxanthine + D-ribose 1-phosphate
show the reaction diagram
P50389
most effective substrate
-
-
?
additional information
?
-
-
substrate specificity
-
-
-
additional information
?
-
-
substrate specificity
-
-
-
additional information
?
-
P50389
substrate specificity, no activity with S-adenosyl-L-methionine
-
-
-
additional information
?
-
-
no activity with S-adenosyl-L-methionine
-
-
-
additional information
?
-
-
no activity with S-adenosylhomocysteine
-
-
-
additional information
?
-
P50389
no activity with S-adenosylhomocysteine
-
-
-
additional information
?
-
-
specificity in both directions of nucleoside cleavage and nucleoside synthesis
-
-
-
additional information
?
-
-
fluorine substitution at the C-2 position of the purine ring increases activity by 50%, whereas substitution with an amino group reduces activity to about one-third of the control
-
-
-
additional information
?
-
-
6-amino purine nucleosides are the preferred substrates, substrate specificity
-
-
-
additional information
?
-
-
replacement of the 6-amino group by an OH-group and of N-7 by a methinic radical results in almost complete loss of activity
-
-
-
additional information
?
-
Q13126
enzyme plays a role in purine and polyamine metabolism and in the regulation of transmethylation reactions
-
-
-
additional information
?
-
P50389
involved in the catabolism of 5'-methylthioadenosine, adenosine, guanosine and inosine
-
-
-
additional information
?
-
-
inverse correlation between enzyme expression and progression of melanocytic tumors, important role of enzyme inactivation in the development of melanomas
-
-
-
additional information
?
-
-
enzyme is involved in the methionine dependent tumor cell growth
-
-
-
additional information
?
-
-
metabolic pathway, overview
-
-
-
additional information
?
-
-
many malignant cells lack MTAP activity because of chromosomal loss or epigeneticregulation
-
-
-
additional information
?
-
-
principal enzyme involved in purine synthesis via the salvage pathway, such that MTAP-negative cancers are solely dependent on de novo purine synthesis mechanisms, intracellular Mtap protein levels determine response to purine biosynthesis inhibitor L-alanosine, overview
-
-
-
additional information
?
-
-
9-[6-deoxy-beta-L-talofuranosyl]-6-methylpurine is a poor substrate for the enzyme
-
-
-
additional information
?
-
-
can not hydrolyze S-adenosylhomocysteine
-
-
-
additional information
?
-
Q7XA67, Q9T0I8
the plant active site is likely less flexible, which may contribute to its reduced efficiency in binding larger substrates. The 5'-alkylthio binding subsite is more constricted in MTAN1
-
-
-
additional information
?
-
Q8U4Q8
PfMTAP is characterized by a broad substrate specificity towards purine nucleosides, with a 20fold higher catalytic efficacy for adenosine and 5'-methylthioadenosine than for inosine and guanosine
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5'-deoxy-5'-(hydroxyethylthio)adenosine + phosphate
adenine + 5-hydroxyethylthio-D-ribose 1-phosphate
show the reaction diagram
-
trypanocidal substrate analogue, preincubation of cells with the substrate lead to 22-37% inhibition of spermidine synthesis from ornithine and 2-7fold increased cytosolic levels of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine, and up to 8fold increased cytosolic level of 5'-methyladenosine
-
-
-
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
salvage reaction
-
-
-
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
involved in cardiac purine breakdown during ischemia
-
-
-
5'-deoxy-5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
substrate is a by-product of polyamine biosynthesis, which is essential for cell growth and proliferation
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
important for the salvage of adenine and methionine
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
an antiproliferative effect on stimulated human lymphocytes and virally transformed mouse fibroblasts
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
involved in salvage of adenine and methionine from 5'-methylthioadenosine
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
involved in salvage of adenine and methionine from 5'-methylthioadenosine
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
Caldariella acidophila
-
physiological significance of 5'-methylthioadenosine cleavage is probably related to removal of the thioether which in turn exerts a significant inhibition on methyl transfer reactions
-
-
-
5'-methylthioadenosine + phosphate
adenine + 5-methylthio-D-ribose 1-phosphate
show the reaction diagram
-
the enzyme regulates ornithine decarboxylase by production of downstream metabolites. Tumor suppressor activity of MTAP may be due to its effect on ornithine decarboxylase activity
-
-
?
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
-
adenosine + phosphate
adenine + D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
-
guanosine + phosphate
guanine + D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
-
S-methyl-5'-thioadenosine + phosphate
adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
S-methyl-5'-thioadenosine + phosphate
adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
-
phosphorolysis
-
-
?
S-methyl-5'-thioadenosine + phosphate
adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
show the reaction diagram
-
recycling of 5'-methylthioadenosine, the byproduct from spermine and spermidine synthesis, to S-adenosylmethionine, the precursor for polyamine synthesis, pathway overview
-
-
?
inosine + phosphate
hypoxanthine + D-ribose 1-phosphate
show the reaction diagram
P50389
-
-
-
-
additional information
?
-
Q13126
enzyme plays a role in purine and polyamine metabolism and in the regulation of transmethylation reactions
-
-
-
additional information
?
-
P50389
involved in the catabolism of 5'-methylthioadenosine, adenosine, guanosine and inosine
-
-
-
additional information
?
-
-
inverse correlation between enzyme expression and progression of melanocytic tumors, important role of enzyme inactivation in the development of melanomas
-
-
-
additional information
?
-
-
enzyme is involved in the methionine dependent tumor cell growth
-
-
-
additional information
?
-
-
metabolic pathway, overview
-
-
-
additional information
?
-
-
many malignant cells lack MTAP activity because of chromosomal loss or epigeneticregulation
-
-
-
additional information
?
-
-
principal enzyme involved in purine synthesis via the salvage pathway, such that MTAP-negative cancers are solely dependent on de novo purine synthesis mechanisms, intracellular Mtap protein levels determine response to purine biosynthesis inhibitor L-alanosine, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
no requirement for metal ion, e.g. Mg2+, Mn2+ or Ca2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+/-)-cis-1-[(9-deazaadenin-9-yl)methyl]-4-ethyl-3-hydroxypyrrolidine
-
-
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(1H-1,2,3-triazol-4-yl)pyrrolidine
-
-
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(penta-3-yl)pyrrolidine
-
-
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-isobutylpyrrolidine
-
-
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-4-ethyl-3-hydroxypyrrolidine
-
-
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-4-ethynyl-3-hydroxypyrrolidine
-
-
(+/-)-trans-4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
(+/-)-trans-4-(cyclohexylmethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
(+/-)-trans-4-allyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
(+/-)-trans-4-butyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
(+/-)-trans-4-cyclopropyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
(+/-)-trans-4-[3-(benzylthio)propyl]-1-[(9-deazaadenin-9-yl)-methyl]-3-hydroxypyrrolidine
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-di-deoxy-1,4-imino-5-methylthio-D-ribitol
Q13126
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-(1-naphthyl)thio-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-(3-methylphenyl)thio-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-(4-methylphenyl)thio-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-methylthio-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-O-methyl-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-phenylthio-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-(2-fluoroethyl)thio-1,4-imino-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-(2-hydroxyethyl)thio-1,4-imino-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-(4-fluorophenyl)thio-1,4-imino-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-ethylthio-1,4-imino-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-n-propylthio-1,4-imino-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-imino-1,4,5,6,7-penta-deoxy-D-ribo-heptitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-1,4-imino-1,4,5-trideoxy-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-5-(3-chlorophenyl)thio-1,4-dideoxy-1,4-imino-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-5-(4-chlorophenyl)thio-1,4-dideoxy-1,4-imino-D-ribitol
-
-
(1S)-1-(9-deazaadenin-9-yl)-5-benzylthio-1,4-dideoxy-1,4-imino-D-ribitol
-
-
(3R,4R)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-methoxymethylpyrrolidine
-
-
(3R,4R)-4-(benzyloxymethyl)-1-[(9-deaza-adenin-9-yl)-methyl]-3-hydroxypyrrolidine
-
-
(3R,4S)-1-[(8-aza-9-deazaadenin-9-yl)methyl]-4-benzylthiomethyl-3-hydroxypyrrolidine hydrochloride
-
-
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-(1-propylthiomethyl)pyrrolidine
-
-
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-(2-propylthiomethyl)pyrrolidine
-
-
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-(4-pyridylthiomethyl)pyrrolidine
-
-
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-phenylthiomethylpyrrolidine
-
-
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-4-(4-fluorophenylthiomethyl)-3-hydroxypyrrolidine
-
-
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-4-ethylthiomethyl-3-hydroxypyrrolidine
-
-
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(1-propyl)pyrrolidine
-
-
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(4-chlorophe-nylthiomethyl)pyrrolidine
Q13126
-
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(methylthiomethyl)pyrrolidine
Q13126
-
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-methylthiomethylpyrrolidine
-
-
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-4-ethyl-3-hydroxypyrrolidine
-
-
(3R,4S)-1-[(9-deazaadenin-9yl)methyl]-3-hydroxy-4-(methylthio-methyl) pyrrolidine
-
treatment of cultured FaDu and Cal27 cells with 0.001 mM (3R,4S)-1-[(9-deazaadenin-9yl)methyl]-3-hydroxy-4-(methylthio-methyl) pyrrolidine and 0.02 mM 5'-methylthioadenosine inhibits MTAP by 96%, increases cellular 5'-methylthioadenosine concentrations, decreases polyamines, and induces apoptosis
(3R,4S)-4-(1-butylthiomethyl)-1-[(9-deaza-adenin-9-yl)-methyl]-3-hydroxypyrrolidine
-
-
(3R,4S)-4-(3-chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
(3R,4S)-4-(4-chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
(3R,4S)-4-benzylthiomethyl-1-[(9-deazaadenin-9-yl)-methyl]-3-hydroxypyrrolidine
-
-
(3R,4S)-4-butyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
(3R,4S)-4-cyclohexylthiomethyl-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
2'-deoxyguanosine
-
-
2'-deoxyinosine
-
weak, competitive
2-bromo-9-(1,3-dihydroxy-2-propoxymethyl)adenine
-
strong
2-bromo-9-(2-hydroxyethoxymethyl)adenine
-
-
2-chloro-9-(1,3-dihydroxy-2-propoxymethyl)adenine
-
strong
2-chloro-9-(2-hydroxyethoxymethyl)adenine
-
-
2-Deoxyribose 1-phosphate
-
-
2-iodo-9-(1,3-dihydroxy-2-propoxymethyl)adenine
-
strong
2-iodo-9-(2-hydroxyethoxymethyl)adenine
-
-
5'-butylthio-DADMe-ImmucillinA
-
inhibits autoinducer-2 production in enterohemorrhagic strain O157:H7 and MTAN knockout strain. Inhibition of autoinducer-2 production in both strains persists for several generations, and causes reduction in biofilm formation. Strong binding to MTAN, causes no growth defects of O157:H7 and MTAN knockout strain in the presence of up to 0.0005 mM, produces the same phenotype as the MTAN- strain
5'-butylthio-DADMe-ImmucillinA
-
inhibits quorum sensing induction completely at 0.001 mM
5'-Chloroformycin
-
-
5'-Deoxy-5'-chloroformycin
-
competitive
5'-Deoxy-5'-methylthiotubercidin
-
-
5'-deoxy-adenosine
-
and analogues; strong, competitive
5'-dimethylthioadenosine
-
sulfonium salt, noncompetitive
5'-dimethylthioadenosine
-
weak
5'-ethylthio-DADMe-ImmucillinA
-
inhibits quorum sensing induction completely at 0.001 mM
5'-Ethylthioadenosine
-
-
5'-methylthio-DADMe-immucillin A
O06401
-
5'-methylthio-DADMe-ImmucillinA
-
inhibits autoinducer-2 production in enterohemorrhagic strain O157:H7 and MTAN knockout strain. Causes no growth defects of O157:H7 and MTAN knockout strain in the presence of up to 0.0005 mM
5'-methylthio-DADMe-ImmucillinA
-
inhibits quorum sensing induction completely at 0.001 mM
5'-methylthio-immucillin-adenine
-
i.e. MT-immucillin-A
-
5'-methylthiotubercidin
-
competitive
5'-methylthiotubercidin
-
-
5'-methylthiotubercidin
-
-
5'-methylthiotubercidin
-
combination of a more occluded active site in its open state and reduced ligand-induced conformational changes in the plant in contrast to Escherichia coli MTAN
5'-methylthiotubercidin
-
active site of apo-MTAN is more open, and greater conformational changes upon ligand binding in contrast to Arabidopsis MTAN1
5'-n-Propylthioadenosine
-
-
9-(phosphonoalkyl)adenine
-
-
-
9-(phosphonoheptyl)adenine
-
-
-
9-[(1-Hydroxy-3-iodo-2-propoxy)methyl]adenine
-
-
9-[(1-Hydroxy-3-iodo-2-propoxy)methyl]adenine
-
competitive
adenine
-
-
adenine
-
strong
adenine
-
competitive; strong
adenine arabinoside
-
weak, competitive
adenosine
-
strong, competitive
calcineurin B-like 3
-
inhibits only in the presence of Ca2+, MTAN interacts specifically with calcineurin B-like 3, but not with calcineurin B-like 1 and calcineurin B-like 4. The 91-amino acid region of calcineurin B-like 3 is sufficient for the interaction with MTAN. Calcineurin B-like 3 and MTAN associate with each other in plant cells, they interact in vitro and in vivo, form a complex outside of the nucleus, colocalize mainly at the plasma membrane
-
dithiothreitol
-
0.8 M, reduction of thermostability
DTNB
-
-
fructose 1-phosphate
-
-
guanidine hydrochloride
-
only recombinant enzyme
Guanine
-
weak
guanosine
-
weak, competitive
hydrogen peroxide
-
reversible inactivation, 60% decrease of enzymatic activity at 0.5 mM hydrogen peroxide
hydrogen peroxide
Q9CQ65
reversible inactivation, 60% decrease of enzymatic activity at 0.5 mM hydrogen peroxide
Inosine
-
weak, competitive
iodoacetamide
-
reversal by dithiothreitol
iodoacetamide
-
no inhibition
iodoacetamide
-
only recombinant enzyme
iodoacetate
-
-
iodoacetate
-
no inhibition
iodoacetate
-
incorporation of 12 mol iodoactate per mol of enzyme
iodoacetate
-
only recombinant enzyme
MT-ImmA
-
i.e. (3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-methylthiomethylpyrrolidine
N-ethylmaleimide
-
5'-methylthioadenosine partly protects
p-chloromercuribenzoic acid
-
strong, partially reversed by dithiothreitol
p-chloromercuribenzoic acid
-
-
p-Cl-PhT-DADMe-ImmA
-
-
proteinase K
-
recombinant enzyme, 10% remaining activity after 4 h at 37C, phosphate protects
-
ribose 1-phosphate
-
-
S-adenosyl-L-homocysteine
-
weak
S-adenosyl-L-homocysteine
-
no inhibition
SH-group blocking compounds
-
inactivation
-
SH-group blocking compounds
-
-
-
Subtilisin
-
recombinant enzyme, 24% remaining activity after 4 h at 37C, phosphate protects
-
tert-butyl hydroperoxide
-
0.01 mM
tert-butyl hydroperoxide
Q9CQ65
0.01 mM
tert-butyl trans-3-hydroxy-4-vinylpyrrolidine-1-carboxylate
-
-
-
trans-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-vinylpyrrolidine
-
-
-
trans-4-cyclopentyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
-
-
L-methionine
-
weak
additional information
Caldariella acidophila
-
no effect by alkylating, mercaptide-forming or oxidizing thiol reagents
-
additional information
-
no inhibition by EDTA, putrescine, cadaverine
-
additional information
-
activity is not affected by alkylating, mercaptide-forming and oxidizing thiol reagents; no inhibition by S-adenosyl-L-methionine
-
additional information
-
promotor hypermethylation strongly reduces enzyme expression
-
additional information
-
structural comparison of MTA phosphorylase and MTA/AdoHcy nucleosidase explains substrate preferences and identifies regions exploitable for inhibitor design
-
additional information
-
Tris buffer severely inhibits the nucleosidase reactions; Tris buffer severely inhibits the nucleosidase reactions
-
additional information
Q9CQ65
MTAP is inactivated in the liver of lipopolysaccharide-challenged mice
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dithiothreitol
-
other thiols are less effective; required
putrescine
-
no effect
putrescine
-
increases activity
SH-group reducing agents
-
requirement
-
SH-group reducing agents
-
requirement
-
spermidine
-
increases activity
spermine
-
increases activity
dithiothreitol
-
required
additional information
-
imidazole buffer is the best buffer, whereas phosphate and HEPES buffers result in enzyme velocities that are only 50-60% of those for imidazole; imidazole buffer is the best buffer, whereas phosphate and HEPES buffers result in enzyme velocities that are only 50-60% of those for imidazole
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.6
2'-deoxy-2'-azido-5'-deoxy-5'-methylthioadenosine
-
-
0.0031
2'-deoxy-5'-deoxy-5'-methylthioadenosine
-
-
0.0039
3'-deoxy-5'-deoxy-5'-methylthioadenosine
-
-
0.009
5'-deoxy-5'-(1,3-thiazol)-2-yl-sulfanyladenosine
-
-
0.005
5'-deoxy-5'-(2-(pyridin-2-yl)ethyl)-thioadenosine
-
-
0.0028
5'-deoxy-5'-(2-methylbutyl)-thioadenosine
-
-
0.002
5'-deoxy-5'-(2-methylphenyl)-thioadenosine
-
-
0.0015
5'-deoxy-5'-(3-methylphenyl)-thioadenosine
-
-
0.0032
5'-deoxy-5'-(4-methoxyphenyl)-thioadenosine
-
-
0.0017
5'-deoxy-5'-(4-methylphenyl)-thioadenosine
-
-
0.0046
5'-deoxy-5'-(phenylethyl)-thioadenosine
-
-
0.0034
5'-deoxy-5'-(phenylmethyl)-thioadenosine
-
-
0.0052
5'-deoxy-5'-(quinolin-2-yl)-sulfanyladenosine
-
-
0.0031
5'-deoxy-5'-butylthioadenosine
-
-
0.00102
5'-deoxy-5'-cyclohexyl-thioadenosine
-
-
0.0035
5'-deoxy-5'-cyclopentyl-thioadenosine
-
-
0.03
5'-deoxy-5'-ethylthioadenosine
-
-
0.004
5'-deoxy-5'-hydroxyethylthioadenosine
-
-
0.003
5'-deoxy-5'-imidazol-2-yl-sulfanyladenosine
-
-
0.0018
5'-deoxy-5'-isobutylthioadenosine
-
-
0.017
5'-deoxy-5'-isopentylthioadenosine
-
-
0.0018
5'-deoxy-5'-methyl-thioadenosine
-
-
0.00001
5'-deoxy-5'-methylthioadenosine
-
-
0.004
5'-deoxy-5'-methylthioadenosine
-
-
0.014
5'-deoxy-5'-methylthioadenosine
-
-
0.026
5'-deoxy-5'-methylthioadenosine
-
-
0.0069
5'-deoxy-5'-phenyl-thioadenosine
-
-
0.00088
5'-deoxy-5'-pyridin-2-yl-sulfanyladenosine
-
-
0.005
5'-deoxy-5'-pyridin-4-yl-sulfanyladenosine
-
-
0.025
5'-deoxy-5'-tert-butylthioadenosine
-
-
0.007
5'-deoxy-5'-[4-(trifluoromethyl)phenyl]-thioadenosine
-
-
0.006
5'-deoxy-adenosine
-
-
0.0043
5'-deoxyadenosine
-
-
0.023
5'-deoxyadenosine
-
-
0.00047
5'-methylthioadenosine
-
-
0.0034
5'-methylthioadenosine
-
-
0.004
5'-methylthioadenosine
-
recombinant enzyme
0.005
5'-methylthioadenosine
-
-
0.005
5'-methylthioadenosine
Q13126
pH 7.0, 25C
0.0055
5'-methylthioadenosine
-
-
0.0055
5'-methylthioadenosine
-
-
0.0071
5'-methylthioadenosine
-
-
0.009
5'-methylthioadenosine
O06401
pH and temperature not specified in the publication, co-substrate: 50 mM phosphate
0.013
5'-methylthioadenosine
-
-
0.024
5'-methylthioadenosine
-
;
0.024
5'-methylthioadenosine
-
recombinant enzyme; wild-type and recombinant enzyme
0.025
5'-methylthioadenosine
-
-
0.0276
5'-methylthioadenosine
-
-
0.0334
5'-methylthioadenosine
-
-
0.095
5'-methylthioadenosine
Caldariella acidophila
-
-
0.147
5'-methylthioadenosine
-
-
0.154
5'-methylthioadenosine
-
pH 7.4, 70C
0.3
5'-methylthioadenosine
-
-
0.008
5-methylthioribose 1-phosphate
-
-
0.023
adenine
-
-
0.0254
adenosine
-
pH 7.4, 70C
0.109
adenosine
-
-
0.184
adenosine
-
-
0.1136
guanosine
-
pH 7.4, 70C
0.916
guanosine
-
-
0.084
Inosine
-
pH 7.4, 70C
0.123
phosphate
-
;
0.125
phosphate
-
recombinant enzyme; wild-type and recombinant enzyme
0.2
phosphate
-
-
0.26
phosphate
O06401
pH and temperature not specified in the publication, co-substrate: 0.2 mM 5'-methylthioadenosine
0.32
phosphate
-
-
0.6
phosphate
-
-
0.75
phosphate
-
recombinant enzyme
3.5
phosphate
-
-
6.1
phosphate
-
-
6.1
phosphate
Caldariella acidophila
-
-
7.5
phosphate
-
-
13.5
phosphate
-
-
0.2009
S-adenosylhomocysteine
-
-
0.005
S-methyl-5'-thioadenosine
-
pH 7.5, 25C
0.963
Inosine
-
-
additional information
additional information
-
nonlinear kinetics with 5'-methylthioadenosine, 2 Km-values, probably due to 2 enzyme activities or 2 interconvertible forms
-
additional information
additional information
-
-
-
additional information
additional information
-
kinetic isotope effects measured on the arsenolysis of 5'-methylthioadenosine catalyzed by the enzyme, the enzyme has a dissociative SN1 transition state with its cationic center at the anomeric carbon and insignificant bond order to the leaving group, the transition state has cationic character at the anomeric carbon and is anionic at the 3'-OH oxygen with an anionic leaving group, late SN1 transition state with significant participation of the phosphate nucleophile, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04
2'-deoxy-2'-azido-5'-deoxy-5'-methylthioadenosine
-
-
0.0004
2'-deoxy-2-fluoro-5'-deoxy-5'-methylthioadenosine
-
-
0.28
2'-deoxy-5'-deoxy-5'-methylthioadenosine
-
-
0.004
3'-deoxy-5'-deoxy-5'-methylthioadenosine
-
-
3.8
5'-deoxy-5'-(1,3-thiazol)-2-yl-sulfanyladenosine
-
-
2.14
5'-deoxy-5'-(2-(pyridin-2-yl)ethyl)-thioadenosine
-
-
5.5
5'-deoxy-5'-(2-methylbutyl)-thioadenosine
-
-
2.4
5'-deoxy-5'-(2-methylphenyl)-thioadenosine
-
-
1.4
5'-deoxy-5'-(3-methylphenyl)-thioadenosine
-
-
1.5
5'-deoxy-5'-(4-methoxyphenyl)-thioadenosine
-
-
0.3
5'-deoxy-5'-(4-methylphenyl)-thioadenosine
-
-
2.5
5'-deoxy-5'-(phenylethyl)-thioadenosine
-
-
2.49
5'-deoxy-5'-(phenylmethyl)-thioadenosine
-
-
3.44
5'-deoxy-5'-(quinolin-2-yl)-sulfanyladenosine
-
-
2.3
5'-deoxy-5'-butylthioadenosine
-
-
1.01
5'-deoxy-5'-cyclohexyl-thioadenosine
-
-
1.57
5'-deoxy-5'-cyclopentyl-thioadenosine
-
-
0.67
5'-deoxy-5'-ethylthioadenosine
-
-
5.9
5'-deoxy-5'-hydroxyethylthioadenosine
-
-
1.5
5'-deoxy-5'-imidazol-2-yl-sulfanyladenosine
-
-
2.9
5'-deoxy-5'-isobutylthioadenosine
-
-
0.85
5'-deoxy-5'-isopentylthioadenosine
-
-
4.6
5'-deoxy-5'-methyl-thioadenosine
-
-
3.16
5'-deoxy-5'-phenyl-thioadenosine
-
-
0.23
5'-deoxy-5'-pyridin-2-yl-sulfanyladenosine
-
-
4.2
5'-deoxy-5'-pyridin-4-yl-sulfanyladenosine
-
-
1.46
5'-deoxy-5'-tert-butylthioadenosine
-
-
0.8
5'-deoxy-5'-[4-(trifluoromethyl)phenyl]-thioadenosine
-
-
4.8
5'-deoxy-adenosine
-
-
0.4
5'-methylthioadenosine
O06401
pH and temperature not specified in the publication, co-substrate: 50 mM phosphate
2
5'-methylthioadenosine
-
-
18.7
5'-methylthioadenosine
-
-
21.4
5'-methylthioadenosine
-
pH 7.4, 70C
24.5
5'-methylthioadenosine
-
-
22.8
adenosine
-
-
43.6
adenosine
-
pH 7.4, 70C
7.31
guanosine
-
-
29.6
guanosine
-
pH 7.4, 70C
9.38
Inosine
-
-
132
Inosine
-
pH 7.4, 70C
0.26
phosphate
O06401
pH and temperature not specified in the publication, co-substrate: 0.2 mM 5'-methylthioadenosine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
588
5'-methylthioadenosine
-
-
400
2600
5'-methylthioadenosine
-
-
400
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000018
(+/-)-cis-1-[(9-deazaadenin-9-yl)methyl]-4-ethyl-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.000002
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(1H-1,2,3-triazol-4-yl)pyrrolidine
-
pH 7.4, 25C
0.0000007
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(penta-3-yl)pyrrolidine
-
pH 7.4, 25C
0.000000047
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-isobutylpyrrolidine
-
pH 7.4, 25C
0.00000084
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-4-ethyl-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.00000039
(+/-)-trans-1-[(9-deazaadenin-9-yl)methyl]-4-ethynyl-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.000000064
(+/-)-trans-4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.000000059
(+/-)-trans-4-(cyclohexylmethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.00000035
(+/-)-trans-4-allyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.000000009
(+/-)-trans-4-butyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.000000063
(+/-)-trans-4-cyclopropyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.000000054
(+/-)-trans-4-[3-(benzylthio)propyl]-1-[(9-deazaadenin-9-yl)-methyl]-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.000026
(1S)-1-(9-deazaadenin-9-yl)-1,4-di-deoxy-1,4-imino-5-methylthio-D-ribitol
Q13126
pH 7.0, 25C
0.00009
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-(1-naphthyl)thio-D-ribitol
-
pH 7.4, 25C
0.00000139
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-(3-methylphenyl)thio-D-ribitol
-
pH 7.4, 25C
0.0000044
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-(4-methylphenyl)thio-D-ribitol
-
pH 7.4, 25C
0.000026
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-methylthio-D-ribitol
-
pH 7.4, 25C
0.000134
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-O-methyl-D-ribitol
-
pH 7.4, 25C
0.0000036
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-phenylthio-D-ribitol
-
pH 7.4, 25C
0.00002
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-(2-fluoroethyl)thio-1,4-imino-D-ribitol
-
pH 7.4, 25C
0.000056
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-(2-hydroxyethyl)thio-1,4-imino-D-ribitol
-
pH 7.4, 25C
0.0000064
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-(4-fluorophenyl)thio-1,4-imino-D-ribitol
-
pH 7.4, 25C
0.0000092
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-ethylthio-1,4-imino-D-ribitol
-
pH 7.4, 25C
0.000004
(1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-5-n-propylthio-1,4-imino-D-ribitol
-
pH 7.4, 25C
0.000044
(1S)-1-(9-deazaadenin-9-yl)-1,4-imino-1,4,5,6,7-penta-deoxy-D-ribo-heptitol
-
pH 7.4, 25C
0.00072
(1S)-1-(9-deazaadenin-9-yl)-1,4-imino-1,4,5-trideoxy-D-ribitol
-
pH 7.4, 25C
0.0000064
(1S)-1-(9-deazaadenin-9-yl)-5-(3-chlorophenyl)thio-1,4-dideoxy-1,4-imino-D-ribitol
-
pH 7.4, 25C
0.000000576
(1S)-1-(9-deazaadenin-9-yl)-5-(4-chlorophenyl)thio-1,4-dideoxy-1,4-imino-D-ribitol
-
pH 7.4, 25C
0.000026
(1S)-1-(9-deazaadenin-9-yl)-5-benzylthio-1,4-dideoxy-1,4-imino-D-ribitol
-
pH 7.4, 25C
0.000085
(3R,4R)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-methoxymethylpyrrolidine
-
pH 7.5, 25C
0.000022
(3R,4R)-4-(benzyloxymethyl)-1-[(9-deaza-adenin-9-yl)-methyl]-3-hydroxypyrrolidine
-
pH 7.5, 25C
0.000055
(3R,4S)-1-[(8-aza-9-deazaadenin-9-yl)methyl]-4-benzylthiomethyl-3-hydroxypyrrolidine hydrochloride
-
pH 7.5, 25C
0.0000013
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-(1-propylthiomethyl)pyrrolidine
-
pH 7.5, 25C
0.0000009
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-(2-propylthiomethyl)pyrrolidine
-
pH 7.5, 25C
0.000014
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-(4-pyridylthiomethyl)pyrrolidine
-
pH 7.5, 25C
0.0000015
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxy-4-phenylthiomethylpyrrolidine
-
pH 7.5, 25C
0.000002
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-4-(4-fluorophenylthiomethyl)-3-hydroxypyrrolidine
-
pH 7.5, 25C
0.00000065
(3R,4S)-1-[(9-deaza-adenin-9-yl)methyl]-4-ethylthiomethyl-3-hydroxypyrrolidine
-
pH 7.5, 25C
0.002
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(1-propyl)pyrrolidine
-
above, pH 7.5, 25C
0.00000036
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(methylthiomethyl)pyrrolidine
Q13126
pH 7.0, 25C
0.0000013
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(methylthiomethyl)pyrrolidine
Q13126
pH 7.0, 25C
0.00000175
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(methylthiomethyl)pyrrolidine
Q13126
pH 7.0, 25C
0.0000017
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-methylthiomethylpyrrolidine
-
pH 7.5, 25C
0.00000031
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-4-ethyl-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.00000028
(3R,4S)-4-(1-butylthiomethyl)-1-[(9-deaza-adenin-9-yl)-methyl]-3-hydroxypyrrolidine
-
pH 7.5, 25C
0.00000081
(3R,4S)-4-(3-chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.5, 25C
0.000002
(3R,4S)-4-(4-chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.5, 25C
0.0000014
(3R,4S)-4-benzylthiomethyl-1-[(9-deazaadenin-9-yl)-methyl]-3-hydroxypyrrolidine
-
pH 7.5, 25C
0.0000000034
(3R,4S)-4-butyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.4, 25C
0.00000076
(3R,4S)-4-cyclohexylthiomethyl-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.5, 25C
0.0002 - 0.0007
2-bromo-9-(1,3-dihydroxy-2-propoxymethyl)adenine
-
-
0.001 - 0.01
2-bromo-9-(2-hydroxyethoxymethyl)adenine
-
-
0.0002 - 0.0007
2-chloro-9-(1,3-dihydroxy-2-propoxymethyl)adenine
-
-
0.001 - 0.01
2-chloro-9-(2-hydroxyethoxymethyl)adenine
-
-
0.0002 - 0.0007
2-iodo-9-(1,3-dihydroxy-2-propoxymethyl)adenine
-
-
0.001 - 0.01
2-iodo-9-(2-hydroxyethoxymethyl)adenine
-
-
0.0083
5'-methylthiotubercidin
-
at 0.005 mM
0.031
5'-methylthiotubercidin
-
-
0.015
9-(phosphonoheptyl)adenine
-
low phosphate concentration of 3.5 mM
-
0.172
adenine
-
-
0.048
Formycin A
-
at 0.05 mM
0.000026
MT-ImmA
-
pH 7.5, 25C
0.00000003
tert-butyl trans-3-hydroxy-4-vinylpyrrolidine-1-carboxylate
-
pH 7.4, 25C
-
0.00000065
trans-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-vinylpyrrolidine
-
pH 7.4, 25C
-
0.000000013
trans-4-cyclopentyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine
-
pH 7.4, 25C
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00000001
5'-butylthio-DADMe-ImmucillinA
-
suppression of light induction in strain BB120
0.000000014
5'-butylthio-DADMe-ImmucillinA
-
suppression of light induction in strain BB170
0.000125
5'-butylthio-DADMe-ImmucillinA
-
in 50 mM phosphate buffer, pH 7.9, 10 mM KCl, at 25C, inhibition of autoinducer-2 production
0.00000011
5'-ethylthio-DADMe-ImmucillinA
-
suppression of light induction in strain BB170
0.00000014
5'-ethylthio-DADMe-ImmucillinA
-
suppression of light induction in strain BB120
0.000025
5'-methylthio-DADMe-immucillin A
O06401
pH and temperature not specified in the publication, in the presence of 10 microM 5'-methylthioadenosine
0.000075
5'-methylthio-DADMe-immucillin A
O06401
pH and temperature not specified in the publication, in the presence of 100 microM 5'-methylthioadenosine
0.000000105
5'-methylthio-DADMe-ImmucillinA
-
suppression of light induction in strain BB120
0.00000094
5'-methylthio-DADMe-ImmucillinA
-
suppression of light induction in strain BB170
0.0006
5'-methylthio-DADMe-ImmucillinA
-
in 50 mM phosphate buffer, pH 7.9, 10 mM KCl, at 25C, inhibition of autoinducer-2 production
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0234
-
purified enzyme
0.0283
-
partially purified enzyme
0.048
-
substrate 2-amino-5'-deoxy-5'-(hydroxyethylthio)adenosine
0.092
-
partially purified enzyme, forward reaction, substrate 5'-methylthioadenosine
0.131
-
purified enzyme
0.17
-
substrate 5'-methyladenosine or 5'-deoxy-5'-(hydroxyethylthio)adenosine
0.25
-
substrate 2-fluoro-5'-deoxy-5'-(hydroxyethylthio)adenosine
0.26
-
substrate 5'-deoxyadenosine, forward reaction
0.365
-
substrate 5'-deoxy-5'-(hydroxyethylthio)adenosine, preincubation with substrate
0.38
-
with adenosine as substrate
0.46
-
with 5'-choroadenosine as substrate
0.67
-
purified enzyme
0.83
-
with 5'-choroadenosine as substrate
0.96
-
with S-adenosylhomocysteine as substrate
1.06
-
with 5'-iodoadenosine as substrate
1.36
-
with 5'-phenylthioadenosine as substrate
1.5
-
with 5'-butylthioadenosine as substrate
1.85
-
with 5'-isobutylthioadenosine as substrate
1.98
-
with 5'-isobutylthioadenosine as substrate
2.12
-
purified enzyme
2.12
-
purified recombinant enzyme
2.44
-
with 5'-phenylthioadenosine as substrate
2.46
Caldariella acidophila
-
purified enzyme
2.48
Caldariella acidophila
-
purified enzyme
2.6
-
with 5'-ethylthioadenosine as substrate
2.72
-
with 5'-butylthioadenosine as substrate
3.14
-
with 5'-iodoadenosine as substrate
4.42
-
with 5'-ethylthioadenosine as substrate
6.25
-
with 5'-methylthioadenosine as substrate
6.35
-
purified enzyme
9.5
-
purified recombinant enzyme
10.2
-
purified enzyme
10.3
-
-
11.5
-
with 5'-methylthioadenosine as substrate
additional information
-
kinetics
additional information
-
substrate specificity
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
O06401
7-7.5 optimal pH
7.1 - 7.6
-
-
7.2
Caldariella acidophila
-
-
7.5
-
assay at
7.5
-
assay at
additional information
Caldariella acidophila
-
pI: 5.2
additional information
-
pI: 5.5
additional information
-
pI: 5.7
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
Caldariella acidophila
-
50% of activity maximum at pH 6.0 and pH 9.0
6.2 - 8.6
-
50% of activity maximum at pH 6.2 and pH 8.6
6.5 - 8.5
-
considerable decrease of activity below pH 6.5 and above pH 8.5
6.5 - 9
O06401
pH 6.5: about 55% of maximal activity, pH 9.0: about 55% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
70
Caldariella acidophila
-
assay at
70
Caldariella acidophila
-
assay at
80
Q8U4Q8
assay at
95
Caldariella acidophila
-
-
100
-
recombinant enzyme; recombinant enzyme
120
-
wild-type enzyme
120
-
; recombinant enzyme
120
-
wild-type enzyme
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 120
-
recombinant enzyme
60 - 120
-
60C: about 40% of maximal activity, 120C: about 40% of maximal activity, recombinant enzyme
86 - 95
Caldariella acidophila
-
86C: 50% of activity maximum, 95C: activity maximum, no activity at 40C
86 - 95
-
2 different activation energy-dependent processes occur below and above 100C
90 - 130
-
90C: about 50% of maximal activity, 130C: about 70% of maximal activity
95 - 140
-
95C: about 50% of maximal activity, 140C: about 45% of maximal activity, wild-type enzyme
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.7
-
isoelectric focusing on polyacrylamide gel in the pH ranges 3-10 and 4.5-6.0
6.54
-
calculation from nucleotide sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
MTAP is not detectable in 39% of chordomas
Manually annotated by BRENDA team
-
diffuse histiocytic lymphoma cell line, possesses no enzyme activity, but intact gene
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
left ventricular specimen
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
left ventricular specimen
-
Manually annotated by BRENDA team
-
cell line derived from metastases of malignant melanomas
Manually annotated by BRENDA team
-
tumor-derived cell line, bladder carcinoma
Manually annotated by BRENDA team
-
peripheral blood
Manually annotated by BRENDA team
-
diffuse, histiocytic
Manually annotated by BRENDA team
-
cell line derived from primary cutaneous melanoma
Manually annotated by BRENDA team
-
cell line derived from metastases of malignant melanomas
Manually annotated by BRENDA team
-
cell line derived from metastases of malignant melanomas
Manually annotated by BRENDA team
-
cell line derived from primary cutaneous melanoma
Manually annotated by BRENDA team
-
low content, cell line derived from primary cutaneous melanoma
Manually annotated by BRENDA team
-
low content, cell line derived from primary cutaneous melanoma
Manually annotated by BRENDA team
-
reduced activity due to hypermethylation of the promotor
Manually annotated by BRENDA team
-
MTAP expression analysis
Manually annotated by BRENDA team
-
SK-Ml-28 cell line derived from metastases of malignant melanomas
Manually annotated by BRENDA team
-
lung fibroblast cell line
Manually annotated by BRENDA team
-
decreased or no expression
Manually annotated by BRENDA team
-
CD34+ erythroid burst-forming unit, granulocyte/monocyte colony-forming unit, granulocyte/erythrocyte/macrophage/megakaryocyte colony-forming unit progenitors and primitive high proliferative potential colony-forming cells in the purified CD34+ cells are cultured
Manually annotated by BRENDA team
-
tumor-derived cell line, Burkitt's lymphoma
Manually annotated by BRENDA team
-
tumor-derived cell line, neuroblastoma
Manually annotated by BRENDA team
-
FC1010 skin fibroblast cell line
Manually annotated by BRENDA team
additional information
-
strongly reduced expression in all melanoma cell lines due to promotor hypermethylation, no enzyme content and expression in melanoma cell line HTZ19d
Manually annotated by BRENDA team
additional information
-
enzyme deficiency in malignant cells, partial or total deletions in the gene of leukemia cell lines of patients with T-cell acute lymphoblastic leukemia
Manually annotated by BRENDA team
additional information
-
enzyme defect is associated with but not responsible for methionine-dependent tumor cell growth
Manually annotated by BRENDA team
additional information
-
wide tissue distribution
Manually annotated by BRENDA team
additional information
-
enzyme is deficient in patients with T-cell acute lymphoblastic leukemia, no activity in enzyme-deficient CEM cells
Manually annotated by BRENDA team
additional information
-
immunohistochemical enzyme expression analysis in tumor tissues, overview
Manually annotated by BRENDA team
additional information
-
MTAP expression analysis
Manually annotated by BRENDA team
additional information
-
no expression in MCF-7, A-549, or U-87 cells
Manually annotated by BRENDA team
additional information
-
A549 cells and MCF-7 cells are MTAP-negative cells
Manually annotated by BRENDA team
additional information
-
RRK081 cells, heterozygous for the MtaplacZ allele
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
cytoplasmic MTAP is not detectable in 39% of chordomas
Manually annotated by BRENDA team
additional information
-
localized at the plasma membrane, in the cytoplasm and in the nucleus of transgenic tobacco plants. Abundant in the membrane structure and weak in the cytoplasm of onion epidermal cells
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Aeropyrum pernix (strain ATCC 700893 / DSM 11879 / JCM 9820 / NBRC 100138 / K1)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Sulfolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2)
Sulfolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2)
Sulfolobus tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
27460
-
sequence analysis
681477
28000
-
-
700813
28450
-
sequence analysis
681477
30000
O06401
SDS-PAGE
723794
54000
-
gel filtration
637545
55000
-
gel filtration
637531
60000
O06401
gel filtration
723794
64000
-
gel filtration
637529
89000
-
gel filtration
637534
90000
-
gel filtration
637541
90000
-
recombinant enzyme, gel filtration
637546
98000
-
gel filtration
637542
98000
-
gel filtration; sedimentation equilibrium
637543
160000
-
gel filtration; gel filtration
637544
160000
-
gel filtration; recombinant enzyme; recombinant enzyme, gel filtration
637549
180000
-
gel filtration
637556
180000
-
gel filtration
658681
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 26000, calculated from sequence
dimer
O06401
2 * 30000, SDS-PAGE
dimer
-
gel filtration
dimer
-
2 * ?, SDS-PAGE
dimer
-
2 * 30300, SDS-PAGE
dimer
-
crystallography
hexamer
-
6 * 27000, SDS-PAGE
hexamer
-
6 * 30000, SDS-PAGE
hexamer
-
6 * 30000, SDS-PAGE
hexamer
-
6 * 27000, recombinant enzyme, SDS-PAGE
hexamer
-
6 * 27000, recombinant enzyme, crystal structure analysis
hexamer
-
dimer-of-trimers with one active site per monomer, crystallization data
hexamer
-
hexamer formed from trimers packed face to face, SsMTAP II is a hexamer formed from trimers packed face to face
trimer
-
3 * 32000, SDS-PAGE
trimer
-
3 * 30000, recombinant enzyme, SDS-PAGE
trimer
-
3 * 32500, SDS-PAGE with addition of 8 M urea and 1% 2-mercaptoethanol
hexamer
-
hexamer formed from trimers packed face to face, SsMTAP II is a hexamer formed from trimers packed face to face
-
additional information
-
enzyme is formed by a trimer of dimers with three symmetric intersubunit disulfide bonds linking the dimers to one another, each monomer contains one active site, which is located near a dimer interface
additional information
-
overall and active site structure, trimer of 3 identical subunits
additional information
-
secondary structure by circular dichroism spectra
additional information
-
base- and methylribose-binding sites
additional information
-
presence of 6 disulfide bonds, organisation in 2 trimers
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with adenine, by sitting- and hanging-drop formation at 22C, at 2.9 A resolution. Belongs to space group P3121, monomer consists of seven alpha-helices, ten beta-strands, and a 3(10)-helix. Residues between 216 and 225 demonstrate weak electron density for both subunits, therefore indicating this loop has high flexibility. Bound adenine is located in the deep pocket formed by the monomer with the entrance partially covered by the adjacent subunit. This flap is critical in the formation of a wide dimer interface
-
MTAN1 in its apo form and in complex with formycin A and 5'-methylthiotubercidin to a resolution of 2.0 A, 1.9 A and 1.8 A, respectively. By hanging-drop, vapor-diffusion technique. Belongs to space group P21. The monomer of MTAN1 has a mixed alpha/beta structure composed of a twisted, ten-stranded mixed beta sheet flanked by seven alpha helices and two short 3(10) helices. In the MTAN1 crystals, the asymmetric unit contains two monomers, which interact via an interface involving the four loops beta2-beta3, beta4-alpha2, beta6-alpha2b and beta8-alpha4, and the alpha2, alpha2b, and alpha5 helices. Both polar and apolar residues are involved in hydrogen bond and van der Waals interactions
-
the intersubunit interface of MTAN is highly hydrophobic and is dominated by van der Waals and hydrophobic interactions
-
crystal structures of apo MTAP and MTAP in complex with p-Cl-PhT-DADMe-ImmA are determined at 1.9 and 2.0 A resolution, respectively. Inhibitor binding causes condensation of the enzyme active site, reorganization at the trimer interfaces, the release of water from the active sites and subunit interfaces, and compaction of the trimeric structure. These structural changes cause the entropy-favored binding of transition state analogues
-
from recombinant enzyme, hanging drop-vapour diffusion method, protein 25 mg/ml, 10 mM Tris-HCl, pH 7.4, 5 mM DTT, 0.4 M NaCl against reservoir solution of 80 mM MES, pH 5.9, 5 mM DTT, 12% w/v polyethylene glycol 6000, 25% v/v ethylene glycol, in presence of substrates adenine, phosphate and sulfate, structure analysis by X-ray diffraction at light scattering
-
X-ray structure with (1S)-1-(9-deazaadenin-9-yl)-1,4-di-deoxy-1,4-imino-5-methylthio-D-ribitol
Q13126
analysis of the crystal packing. Space group is C2, unit-cell parameters are a = 135.16, b = 138.09, c = 96.56 A, beta = 92.21. The asymmetric unit contains two independent half-hexamers, the other half of each of which is generated by a crystallographic twofold axis; the structure of SsMTAP II is originally determined in space group P1 and shows R32 pseudosymmetry. Post-analysis using phenix.xtriage shows that the correct space group is C2. The structure refined in space group C2 is reported and the factors that initially led to the incorrect space-group assignment are discussed
-
crystals are grown at either room temperature or 18C using the hanging drop vapor diffusion technique. Determination of the structure of 5'-deoxy-5'-methylthioadenosine phosphorylase alone, as ternary complexes with sulfate plus substrates 5'-deoxy-5'-methylthioadenosine, adenosine, or guanosine, or with the noncleavable substrate analog formycin B and as binary complexes with phosphate or sulfate alone. The structure of unliganded SsMTAP is refined at 2.5 A resolution and the structures of the complexes are refined at resolutions ranging from 1.6 A to 2.0 A
-
from recombinant enzyme, hanging drop-vapour diffusion method, protein solution, 7-10 mg/ml, 18C, reservoir solution for native crystals: Tris-HCl 10 mM, pH 7.4, 28-30% dioxane, 12% 2-methyl-2,4-pentanediol, 0.12 M MgCl2, 0,04 M NaCl, for crystals of enzyme complexed with substrates or sulfate and phosphate ions, substrates are added and NaCl is exchanged for MgSO4 or NH4Cl and KH2PO4, respectively, X-ray structure determination and analysis
-
hanging-drop, vapor-diffusion method at 22C, the crystal structure of the enzyme in complex with 5'-deoxy-5'-methylthioadenosine and sulfate is determined to 1.45 A resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
O06401
4h, 40% loss of activity
723794
37
O06401
4h, 90% loss of activity
723794
40 - 55
-
15 min, stable
637542
65
-
rapid inactivation
637540
70
-
15 min, complete loss of activity
637542
70
-
recombinant enzyme, 0.8 M DTT, stable
637549
90
-
recombinant enzyme, 0.8 M DTT, 2 h, loss of 38% activity
637549
90
-
1 h, wild-type enzyme is completely stable, mutant enzyme C262S loses 32% of its activity, mutant enzyme c259S/C261A loses 63% of its activity
658681
100
Caldariella acidophila
-
1 h, stable
637527
100
-
stable for at least 2 h
637530
100
Caldariella acidophila
-
1 h, stable
637539
100
-
stable for at least 2 h
637544
100
-
1 h, 15% loss of activity of recombinant enzyme, wild-type enzyme remains stable; recombinant enzyme, 1 h, 85% remaining activity
637549
100
-
recombinant enzyme, 1 h, 95% remainig activity in presence of 100 mM phosphate
637554
100
-
2 h, stable
637555
100
-
5 h, 98% remaining activity
637556
102
-
apparent Tm, mutant enzyme C259S/C261S
658681
106
-
apparent Tm, mutant enzyme C262S
658681
110
-
recombinant enzyme, 10 min, 50% remaining activity in absence and 90% remaining activity in presence of 100 mM phosphate
637554
110
-
recombinant enzyme, 2 h, stable
637555
111
-
melting temperature of recombinant enzyme; recombinant enzyme, melting temperature
637549
112
-
apparent Tm, wild-type enzyme
658681
118
-
recombinant enzyme in presence of 100 mM phosphate, melting temperature
637549
120
-
2 h, stable
637544
120
-
recombinant enzyme, 10 min, no activity in absence and 50% remaining activity in presence of 100 mM phosphate
637554
120
-
-
637555
130
-
half-life: 15 min
637530
130
-
half-inactivation time: 15 min; half-life: 15 min
637544
130
-
half-life: 43 min
637556
132
-
10 min, melting temperature
637530, 637544
137
-
melting temperature
637556
139
-
melting temperature in presence of 100 mM phosphate
637556
140
-
half-life: 5 min
637530
140
-
half-inactivation time: 5 min; half-life: 5 min
637544
140
-
half-life: 13 min
637556
145
-
half-life: 5 min
637556
additional information
-
high degree of thermal stability
637529
additional information
-
resistance to thermal inactivation is increased remarkably by addition of 5'-methylthioadenosine or phosphate
637542
additional information
-
the recombinant 5'-methylthioadenosine phosphorylase is less thermophilic and thermostable than the Sulfolobus solfataricus enzyme, since an incorrect positioning of disulfide bonds within the molecule generates structures less stable to thermal unfolding; the recombinant enzyme, expressed in Escherichia coli, is less thermostable and thermophilic than the native enzyme due to incorrect positioning of disulfide bonds
637549
additional information
-
disulfide linkages play a key role in thermal stability
637555
additional information
Q8U4Q8
PfMTAP is a highly thermostable protein
721717
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
rapid inactivation in absence of reducing agents: 50% inactivation within 24 h at both 4C and -20C
-
resistance to thermal inactivation is increased remarkably by addition of 5'-methylthioadenosine or phosphate
-
Stable to freeze-thawing
-
dithiothreitol 0.8 M, reduction of thermostability
-
enzyme is extremely stable to proteolytic cleavage
-
transition midpoint for guanidinium chloride-induced unfolding is 3.0 M after 22 h incubation. The value decreases to 2.0 M in presence of 30 mM dithiothreitol. The guanidinium chloride-induced unfolding is completely reversible
-
after 40 min exposure to 10.4 GHz microwave radiation at 90C the enzyme retains 78% activity compared to a control incubated at the same temperature without irradiation. KCl or NaCl increases the susceptibility to microwave irradiation. Protection against microwave inactivation by phosphate or sulfate.
-
no loss of activity after 24 h at room temperature in presence of 9 M urea, 4 M guanidine hydrochloride, 0.075% SDS, 50% methanol, 50% ethanol, 50% dimethylformamide, 1 M NaCl, and 1% Triton X-100
-
no loss of activity after treatment with thermolysin, trypsin, and chymotrypsin for 24 h at 37C
-
phosphate, and less efficiently also arsenate and sulfate, stabilize the recombinant enzyme against inactiviation by temperature, SDS, urea, and proteolytic enzymes
-
recombinant enzyme, 90C in 2% SDS, 30 min, loss of 60% activity
-
recombinant enzyme, 90C in 8 M urea, 30 min, loss of 70% activity
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
1-propanol
-
at 50%: 88% remaining activity after 60 min at 50C, 58% remaining activity after 60 min at 70C, 22% remaining activity after 60 min at 90C
1-propanol
-
no loss of activity after 24 h at room temperature in presence of 50% methanol, loss of 90% activity at 90C after 1 h
acetonitrile
-
loss of 89% activity at 70C after 1 h
acetonitrile
-
at 50%: stable at 90C for 30 min, loss of 62% activity after 60 min
dimethylformamide
-
at 50%: 48% remaining activity after 60 min at 50C, 5% remaining activity after 60 min at 70C, no activity at 90C
dimethylformamide
-
no loss of activity after 24 h at room temperature in presence of 50% dimethylformamide, loss of 21% activity at 90C after 1 h
Ethanol
-
at 50%: 90% remaining activity after 60 min at 50C, 65% remaining activity after 60 min at 70C, 30% remaining activity after 60 min at 90C
Ethanol
-
no loss of activity after 24 h at room temperature in presence of 50% ethanol, loss of 88% activity at 90C after 1 h, 50%, 24 h at room temperature, no loss of activity
guanidine-HCl
-
4 M, 24 h at room temperature, no loss of activity
Methanol
-
at 50%: stable at 90C for 30 min, loss of 77% activity after 60 min
Methanol
-
no loss of activity after 24 h at room temperature in presence of 50% methanol, loss of 80% activity at 90C after 1 h, 50%, 24 h at room temperature, no loss of activity
N,N-dimethylformamide
-
50%, 24 h at room temperature, no loss of activity
SDS
-
0.075%, 24 h at room temperature, no loss of activity. After 60 min of incubation in 2% SDS the enzyme remains fully active at 70C and retains 20% residual activity at 90C. Complete inactivation after 5 min at 100C in 0.5% SDS
tetrahydrofuran
-
loss of 76% activity at 70C after 30 min, complete loss of activity after 1 h at 70C
tetrahydrofuran
-
at 50%: 77% remaining activity after 60 min at 50C, 50% remaining activity after 60 min at 70C, 3% remaining activity after 60 min at 90C
Triton X-100
-
9 M, 24 h at room temperature, no loss of activity
urea
-
9 M, 24 h at room temperature, no loss of activity
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
O2 partially inactivates
-
637540
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, stable for several months
Caldariella acidophila
-
-20C, 5 mM DTT, 50 mM potassium phosphate, pH 7.4, less than 10% loss of activity after 1 month
-
-20C, stable
O06401
20C, Tris-HCl 10 mM, pH 7.4, purified enzyme, stable for at least 1 year
-
-20C, stable for at least 3 weeks
-
-70C, stable for at least 4 months
-
-20C, 10 mM Tris-HC1, pH 7.4, containing 1 mM EDTA, stable for at least 1 year
-
-20C, purified enzyme, Tris-HCl 10 mM, pH 7.4, 1 mM EDTA, stable at least 1 year
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
as a GST fusion form, by gel filtration
-
by centrifugation and on Ni-NTA column and by gel filtration; on Ni-NTA column
-
by ultrasonication, centrifugation, gel filtration and anion exchange chromatography, to homogeneity; by ultrasonication, centrifugation, gel filtration and anion exchange chromatography, to homogeneity
-
-
Caldariella acidophila
-
Ni2+-Sepharose column chromatography
-
recombinant from Escherichia coli
-
recombinant His-tagged enzyme from Escherichia coli
-
Ni2+-Sepharose column chromatography
Q9CQ65
recombinant enzyme
-
from lung; partial
-
recombinant enzyme; recombinant from Escherichia coli
-
recombinant from Escherichia coli
-
using heat-treatment and MTA-Sepharose chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
different regions of MTAN cloned into the pGBT9.BS vector and transformed into Y190 yeast cells carrying pGAD.GH or pGAD.CBL3. Expressed in Escherichia coli BL21 cells carrying a GST fusion construct. MTAN promoter-GUS construct (pBI.tMTAN) transformed into Agrobacterium tumefaciens strain GV3101 and introduced into Arabidopsis plants by the floral dip method. 35S::CFP-CBL3-Myc and 35S::YFP-MTANHA constructs introduced, either alone or in combination, into Nicotiana benthamiana leaves by Agrobacterium tumefaciens-mediated infiltration method. CBL3-GFP and MTAN-GFP chimeric genes under the control of the cauliflower mosaic virus 35S promoter (pMD.CBL3 and pMD.MTAN) transiently expressed in Allium cepa epidermal cells. Onion epidermal cells bombarded with fusion constructs CBL3-YN and MTAN-YC
-
into pGEX-4T3 vector and overexpressed in Escherichia coli BL21 (DE3) RIL; into pGEX-4T3 vector and overexpressed in Escherichia coli BL21 (DE3) RIL
-
into the pET28a+ vector at the NdeI and HindIII sites, overexpression of the enzyme with a cleavable N-terminal His6 tag in Escherichia coli BL21 Codon+ cells; into the pET28a+ vector at the NdeI and HindIII sites, overexpression of the enzyme with a cleavable N-terminal His6 tag in Escherichia coli BL21 Codon+ cells
-
expressed in cutaneous squamous cell carcinoma cells
-
expressed in Drosophila melanogaster and Mus musculus
-
expressed in Escherichia coli BL21(DE3) cells
-
expression of His-tagged protein in Escherichia coli BL21(DE3) cells
-
expression of the N-terminally His6-tagged enzyme in Escherichia coli
-
from cells of patients with T-cell acute lymphoblastic leukemia, DNA sequence analysis, 9p21 chromosome, topologic map
-
functional expression in enzyme deficient cell line MCF-7
-
gene MTAP, located f100 kb telomeric to the p16INK4A/CDKN2A gene on chromosome 9p21, expression in HuCCT1 and SNU308 cell lines, the enzyme expression does not affect the cells
-
quantitative PCR, RNA mutational analysis, analysis of methylation status of the enzymes promotor; re-expression in Mel Im cell line
-
the gene maps on the 9p21 chromosome, strictly linked to the tumor suppressor gene p16INK4A, functional expression in Escherichia coli strain JM105
-
wild-type and promotor deletion mutant, expression in HeLa cells, luciferase reporter assay
-
expressed in Escherichia coli BL21(DE3) cells
Q9CQ65
RRK081 embryonic stem cells, containing a gene-trap vector inserted between exon 3 and exon 4 of the mouse Mtap locus (MtaplacZ) injected into mouse blastocysts derived from C57BL/6 animals, embryos implanted in pseudopregnant females
-
expressed in Escherichia coli
O06401
expressed in Escherichia coli
Q8U4Q8
expression in Escherichia coli
-
expression of MTAP in MTAP-deleted MCF-7 breast adenocarcinoma cells results in a significant reduction of ODC activity
-
expression at a high level in Escherichia coli; overexpression in Escherichia coli strain RB791, amino acid determination, incorrect positioning of disulfide bonds, the recombinant enzyme is less thermostable and thermophilic than the native enzyme
-
expression in Escherichichia coli
-
overexpression in Escherichia coli BL21
-
overexpression in Escherichia coli strain RB791, amino acid determination, incorrect positioning of disulfide bonds, the recombinant enzyme is less thermostable and thermophilic than the native enzyme
-
recombinant SsMTAPII and its C262S and C259S/C261S mutant forms are expressed in Escherichia coli BL21 (lDE3) cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
loss of MTAP expression is significantly correlated with loss of CDKN2A
-
lymphoma-infiltrated tissues tend to have reduced levels of Mtap mRNA and MTAP protein in addition to unaltered levels of methyldeoxycytidine. Loss of MTAP expression is independent from loss of CDKN2A expression
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F135L
-
can reduce steric hindrance at the end of the 5'-alkylthio binding subsite, so that longer 5'-substituents may be accommodated more easily in the MTAN2 active site
F148L
-
can reduce steric hindrance at the end of the 5'-alkylthio binding subsite
I132V
-
no significant structural change
I145V
-
no significant structural change
L168M
-
has a more extended side chain, may affect the binding of ligands at the 5'-alkylthio position
L181M
-
has a more extended side chain, may affect the binding of ligands at the 5'-alkylthio position
C136S
-
mutant is insensitive to oxidative inhibition
V56I
-
natural polymorphism present in 7 of 9 melanoma cell lines, not in SK-Mel-28 and in HTZ19d
C136S
Q9CQ65
mutant is insensitive to oxidative inhibition
C223S
Q9CQ65
mutant is insensitive to oxidative inhibition
C259S/C261S
-
mutant enzyme shows thermophilic and thermostable features significantly lower than those of the wild-type enzyme
C259S/C261S
-
in contrast wo wild-type C262S and C259S/C261S mutants show complete thermal denaturation curves with sigmoidal transitions centered at 102C and 99C respectively. Under reducing conditions these values decrease by 4C and 8C respectively, highlighting the important role exerted by the CXC disulfide on enzyme thermostability. The double mutant (the mutant lacking the structural CXC motif), has more impact on the thermostability of SsMTAPII than the single mutant
C262S
-
mutant enzyme shows thermophilic and thermostable features significantly lower than those of the wild-type enzyme
C262S
-
in contrast wo wild-type C262S and C259S/C261S mutants show complete thermal denaturation curves with sigmoidal transitions centered at 102C and 99C respectively. Under reducing conditions these values decrease by 4C and 8C respectively, highlighting the important role exerted by the CXC disulfide on enzyme thermostability
C223S
-
mutant is insensitive to oxidative inhibition
additional information
-
cell line DHL-9 contains a promotor sequence with a deletion of 14 bases, the deletion mutant allele is widespread throughout the japanese population and not responsible for the enzyme deficiency in this cell line
additional information
-
melanoma cell line HTZ19d is a deletion mutant without enzyme expression and activity
additional information
-
knockdown of Mtap protein by RNA interference in L-alanosine-resistant HuCCT1 cells conferred sensitivity to this agent, L-alanosine shows robust growth inhibition in MTAP-negative biliary cancer cell lines CAK-1 and GBD-1 accompanied by striking depletion of intracellular ATP and failure to rescue this depletion via addition of exogenous methylthioadenosine, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
guanidinium chloride-induced unfolding is completely reversible
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
potential of MTAN as target for bacterial anti-infective drug design
drug development
Escherichia coli O157:H7 EDL933
-
potential of MTAN as target for bacterial anti-infective drug design
-
analysis
-
methylthioadenosine phosphorylase protein expression may be a predictive marker of interferon therapy resistance in patients with melanoma and disease progression
diagnostics
-
methylthioadenosine phosphorylase protein expression may be a predictive marker of interferon therapy resistance in patients with melanoma and disease progression
drug development
-
combination of 5'-methylthioadenosine with clinical cancer drugs 5-fluorouracil or 6-thioguanine, in the treatment of MTAP-negative tumors, may produce a significantly improved therapeutic index
drug development
-
loss of MTAP activity in a subset of chordomas suggests that this group of patients may benefit from chemoselective inhibition of the de novo purine synthesis pathway. Purine synthesis inhibitors may be considered for chordoma patients with MTAP-deficient tumours
medicine
-
gene is linked to the important tumor suppressor gene p16INK4A, enzyme is of key importance in defining the chromosomal area homozygously deleted in a large number of human tumors, absence of enzyme activity only in malignant cells is of great value in developing selective antitumor therapeutic strategies
medicine
-
possibility of targeting the enzyme in the design of an enzyme-selective therapy for patients with T-cell acute lymphoblastic leukemia and other enzyme-deficient malignancies
medicine
-
enzyme is a potential chemotherapeutic target
drug development
-
potential of MTAN as target for bacterial anti-infective drug design