ホスホリボシルアミノイミダゾールカルボキサミドホルミルトランスフェラーゼ
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/07 23:42:55」(JST)
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| phosphoribosylaminoimidazolecarboxamide formyltransferase |
| Identifiers |
| EC number |
2.1.2.3 |
| CAS number |
9032-03-5 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
|
In enzymology, a phosphoribosylaminoimidazolecarboxamide formyltransferase (EC 2.1.2.3), also known by the shorter name AICAR transformylase, is an enzyme that catalyzes the chemical reaction
- 10-formyltetrahydrofolate + AICAR tetrahydrofolate + FAICAR
Thus, the two substrates of this enzyme are 10-formyltetrahydrofolate and AICAR, whereas its two products are tetrahydrofolate and FAICAR.
This enzyme participates in purine metabolism and one carbon pool by folate.
Nomenclature
This enzyme belongs to the family of transferases that transfer one-carbon groups, specifically the hydroxymethyl-, formyl- and related transferases. The systematic name of this enzyme class is 10-formyltetrahydrofolate:5-phosphoribosyl-5-amino-4-imidazole-carb oxamide N-formyltransferase. Other names in common use include:
- 10-formyltetrahydrofolate:5-phosphoribosyl-5-amino-4-imidazolecarboxamide formyltransferase
- 5-amino-1-ribosyl-4-imidazolecarboxamide 5-phosphate,
- 5-amino-4-imidazolecarboxamide ribonucleotide transformylase,
- 5-amino-4-imidazolecarboxamide ribotide transformylase,
- 5-phosphoribosyl-5-amino-4-imidazolecarboxamide formyltransferase,
- AICAR formyltransferase,
- AICAR transformylase,
- aminoimidazolecarboxamide ribonucleotide transformylase, and
- transformylase.
Structural studies
As of late 2007, 11 structures have been solved for this class of enzymes, with PDB accession codes 1G8M, 1M9N, 1OZ0, 1P4R, 1PKX, 1PL0, 1THZ, 2B1G, 2B1I, 2IU0, and 2IU3.
References
- HARTMAN SC, BUCHANAN JM (1959). "Biosynthesis of the purines. XXVI. The identification of the formyl donors of the transformylation reactions". J. Biol. Chem. 234 (7): 1812–6. PMID 13672969.
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Transferase: one carbon transferases (EC 2.1)
|
|
| 2.1.1: Methyl- |
| N- |
- Histamine N-methyltransferase
- Phenylethanolamine N-methyltransferase
- Amine N-methyltransferase
- Phosphatidylethanolamine N-methyltransferase
|
|
| O- |
- 5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase
- Catechol-O-methyl transferase
|
|
| Homocysteine |
- Betaine-homocysteine methyltransferase
- Homocysteine methyltransferase
- Methionine synthase
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|
| Other |
- Phosphatidyl ethanolamine methyltransferase
- DNMT3B
- Histone methyltransferase
- Thymidylate synthase
- DNA methyltransferase
- Thiopurine methyltransferase
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|
|
2.1.2: Hydroxymethyl-,
Formyl- and Related |
| Hydroxymethyltransferase |
- Serine hydroxymethyltransferase
- 3-methyl-2-oxobutanoate hydroxymethyltransferase
|
|
| Formyltransferase |
- Phosphoribosylglycinamide formyltransferase
- Inosine monophosphate synthase
|
|
| Other |
- Glutamate formimidoyltransferase
- Aminomethyltransferase
|
|
|
2.1.3: Carboxy-
and Carbamoyl |
| Carboxy |
- methylmalonyl-CoA carboxytransferase
|
|
| Carbamoyl |
- Aspartate carbamoyltransferase
- Ornithine carbamoyltransferase
- Oxamate carbamoyltransferase
- Putrescine carbamoyltransferase
- 3-hydroxymethylcephem carbamoyltransferase
- Lysine carbamoyltransferase
- N-acetylornithine carbamoyltransferase
|
|
|
| 2.1.4: Amidine |
- Arginine:glycine amidinotransferase
|
|
- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15-99
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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Proteins: enzymes
|
|
| Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
- Enzyme kinetics
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
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| Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
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| Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
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|
| Types |
- EC1 Oxidoreductases(list)
- EC2 Transferases(list)
- EC3 Hydrolases(list)
- EC4 Lyases(list)
- EC5 Isomerases(list)
- EC6 Ligases(list)
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- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15-99
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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UpToDate Contents
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- 1. 悪性腹膜中皮腫：治療 malignant peritoneal mesothelioma treatment
English Journal
- Amino-4-Imidazolecarboxamide Ribotide Directly Inhibits Coenzyme A Biosynthesis in Salmonella enterica.
- Bazurto JV, Downs DM.Author information Department of Microbiology, University of Georgia, Athens, Georgia, USA.AbstractAminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a by-product of histidine biosynthesis. In bacteria, yeast, and humans, accumulation of AICAR has been shown to affect an array of cellular processes by both direct and indirect mechanisms. In purine biosynthesis, AICAR is the substrate of the bifunctional protein phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase (PurH, EC 2.1.2.3/3.5.4.10). Strains lacking PurH accumulate AICAR and have a defect in the synthesis of the 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) moiety of thiamine. The formation of HMP is also compromised in vivo when coenzyme A (CoA) levels are reduced. Our results show that the in vivo accumulation of AICAR decreased total CoA pools and, further, that AICAR inhibited the activity of pantoate β-alanine ligase in vitro (PanC, EC 6.3.2.1). These results demonstrated a mechanism of AICAR action and provide new insights into the metabolic consequences of disrupting purine metabolism.
- Journal of bacteriology.J Bacteriol.2014 Feb;196(4):772-9. doi: 10.1128/JB.01087-13. Epub 2013 Dec 2.
- Aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a by-product of histidine biosynthesis. In bacteria, yeast, and humans, accumulation of AICAR has been shown to affect an array of cellular processes by both direct and indirect mechanisms. In purine biosynthesis,
- PMID 24296672
- Biological and structural evaluation of 10R- and 10S-methylthio-DDACTHF reveals a new role for sulfur in inhibition of glycinamide ribonucleotide transformylase.
- Connelly S, DeMartino JK, Boger DL, Wilson IA.Author information Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.AbstractGlycinamide ribonucleotide transformylase (GAR Tfase) is a folate-dependent enzyme in the de novo purine biosynthesis pathway, which has long been considered a potential target for development of anti-neoplastic therapeutics. Here we report the biological and X-ray crystallographic evaluations of both independent C10 diastereomers, 10S- and 10R-methylthio-DDACTHF, bound to human GAR Tfase, including the highest-resolution apo GAR Tfase structure to date (1.52 Å). Both diastereomers are potent inhibitors (Ki = 210 nM for 10R, and Ki = 180 nM for 10S) of GAR Tfase and exhibit effective inhibition of human leukemia cell growth (IC₅₀ = 80 and 50 nM, respectively). Their inhibitory activity was surprisingly high, and these lipophilic C10-substituted analogues show distinct advantages over their hydrophilic counterparts, most strikingly in retaining potency in mutant human leukemia cell lines that lack reduced folate carrier protein activity (IC₅₀ = 70 and 60 nM, respectively). Structural characterization reveals a new binding mode for these diastereoisomers, in which the lipophilic thiomethyl groups penetrate deeper into a hydrophobic pocket within the folate-binding site. In silico docking simulations of three other sulfur-containing folate analogues also indicate that this hydrophobic cleft represents a favorable region for binding lipophilic substituents. Overall, these results suggest sulfur and its substitutions play an important role in not only the binding of anti-folates to GAR Tfase but also the selectivity and cellular activity (growth inhibition), thereby presenting new possibilities for the future design of potent and selective anti-folate drugs that target GAR Tfase.
- Biochemistry.Biochemistry.2013 Jul 30;52(30):5133-44. doi: 10.1021/bi4005182. Epub 2013 Jul 19.
- Glycinamide ribonucleotide transformylase (GAR Tfase) is a folate-dependent enzyme in the de novo purine biosynthesis pathway, which has long been considered a potential target for development of anti-neoplastic therapeutics. Here we report the biological and X-ray crystallographic evaluations of bo
- PMID 23869564
- Fibroblasts from methotrexate-sensitive mice accumulate methotrexate polyglutamates but those from methotrexate-resistant mice do not.
- You X, Williams A, Dervieux T, He W, Cronstein BN.Author information Division of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. xn_you@yahoo.comAbstractOBJECTIVES: We and others have previously demonstrated that methotrexate (MTX) mediates its anti-inflammatory effects through an increase in cellular release of adenosine. Consistent with this observation, there is no increase in adenosine from exudates of mouse strains resistant to MTX. Because intracellular MTX polyglutamates inhibit AICAR transformylase (ATIC) activity and thereby promote adenosine release we determined whether there is any difference in the capacity of cells from MTX-resistant mice to accumulate MTX polyglutamates.
- Clinical and experimental rheumatology.Clin Exp Rheumatol.2013 May-Jun;31(3):433-5. Epub 2013 Mar 4.
- OBJECTIVES: We and others have previously demonstrated that methotrexate (MTX) mediates its anti-inflammatory effects through an increase in cellular release of adenosine. Consistent with this observation, there is no increase in adenosine from exudates of mouse strains resistant to MTX. Because int
- PMID 23464989
Japanese Journal
- THE OCCURRENCE AND PROPERTIES OF METHYLENE-TETRAHYDROFOLATE DEHYDROGENASE IN PEA SEEDLINGS, AND INTRACELLULAR DISTRIBU-TION OF SOME FOLATE-LINKED ENZYMES IN THE PLANT
Related Links
- "Phosphoribosylaminoimidazolecarboxamide Formyltransferase" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH ... An enzyme that catalyzes the conversion of aminoimidazole-4 ...
- Phosphoribosylaminoimidazolecarboxamide Formyltransferase information including symptoms, causes, diseases, symptoms, treatments, and other medical and health issues. ... Introduction ...
★リンクテーブル★
[★]
- 英
- phosphoribosylaminoimidazolecarboxamide formyltransferase