2-イソプロピルリンゴ酸合成酵素、2-イソプロピルリンゴ酸シンターゼ
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/19 12:48:25」(JST)
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| 2-isopropylmalate synthase |
| Identifiers |
| EC number |
2.3.3.13 |
| CAS number |
9030-98-2 |
| 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 2-isopropylmalate synthase (EC 2.3.3.13) is an enzyme that catalyzes the chemical reaction
- acetyl-CoA + 3-methyl-2-oxobutanoate + H2O (2S)-2-isopropylmalate + CoA
The three substrates of this enzyme are acetyl-CoA, 3-methyl-2-oxobutanoate, and H2O, and its products are (2S)-2-isopropylmalate and CoA.
The enzyme belongs to the family of transferases, specifically those acyltransferases that convert acyl groups into alkyl groups on transfer. The systematic name of this enzyme class is acetyl-CoA:3-methyl-2-oxobutanoate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming). Other names in common use include 3-carboxy-3-hydroxy-4-methylpentanoate 3-methyl-2-oxobutanoate-lyase, (CoA-acetylating), alpha-isopropylmalate synthetase, alpha-isopropylmalate synthase, alpha-isopropylmalic synthetase, isopropylmalate synthase, and isopropylmalate synthetase. This enzyme participates in biosynthesis of L-leucine and pyruvate metabolism. Monovalent and divalent cation activation have been reported for enzymes from different sources. [1][2][3]
Mycobacterium tuberculosis α-isopropylmalate synthase requires a divalent metal ion, of which Mg2+ and Mn2+ give highest activity, and a monovalent cation, with K+ as the best activator.[4][5] Zn2+ was shown to be an inhibitor, contrary to what was assumed from the structural data. In addition to the complex requirements for a divalent metal and further activation by K+, M. tuberculosis α-isopropylmalate synthase follows a random kinetic mechanism for catalysis.[citation needed] Another feature of the M. tuberculosis homolog is that L-leucine, the feedback inhibitor, inhibits the enzyme in a time-dependent fashion. This was the first demonstration of a feedback inhibitor that displays slow-onset inhibition.[6]
Structural studies
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code 1SR9.
References
- ^ Cole FE, Kalyanpur MG, Stevens CM (1973). "Absolute configuration of alpha isopropylmalate and the mechanism of its conversion to beta isopropylmalate in the biosynthesis of leucine". Biochemistry. 12 (17): 3346–50. doi:10.1021/bi00741a031. PMID 4270046.
- ^ Kohlhaw G, Leary TR, Umbarger HE (1969). "Alpha-isopropylmalate synthase from Salmonella typhimurium Purification and properties". J. Biol. Chem. 244 (8): 2218–25. PMID 4976555.
- ^ Webster RE and Gross, SR (1965). "The alpha-isopropylmalate synthetase of Neurospora. I. The kinetics and end product control of alpha-isopropylmalate synthetase function". Biochemistry 4 (11): 2309–2327. doi:10.1021/bi00887a008.
- ^ Carvalho LP, Blanchard, JS (2006). "Kinetic and Chemical Mechanism of alpha-Isopropylmalate Synthase from Mycobacterium tuberculosis". Biochemistry. 45 (29): 8988–99. doi:10.1021/bi0606602. PMC 2507874. PMID 16846242.
- ^ Carvalho LP, Blanchard, JS (2006). "Kinetic analysis of the effects of monovalent cations and divalent metals on the activity of Mycobacterium tuberculosis alpha-isopropylmalate synthase". Archives of Biochemistry and Biophysics. 451 (2): 141–48. doi:10.1016/j.abb.2006.03.030. PMID 16684501.
- ^ Carvalho LP, Argyrou A, Blanchard, JS (2005). "Slow-onset Feedback Inhibition: Inhibition of Mycobacterium tuberculosis alpha-Isopropylmalate Synthase by L-Leucine". Journal of the American Chemical Society. 127 (28): 10004–5. doi:10.1021/ja052513h. PMID 16011356.
UpToDate Contents
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English Journal
- Improving Functional Annotation in the DRE-TIM Metallolyase Superfamily through Identification of Active Site Fingerprints.
- Kumar G1, Johnson JL1, Frantom PA1.
- Biochemistry.Biochemistry.2016 Mar 29;55(12):1863-72. doi: 10.1021/acs.biochem.5b01193. Epub 2016 Mar 18.
- PMID 26935545
- A Feedback-Insensitive Isopropylmalate Synthase Affects Acylsugar Composition in Cultivated and Wild Tomato.
- Ning J1, Moghe GD1, Leong B1, Kim J1, Ofner I1, Wang Z1, Adams C1, Jones AD1, Zamir D1, Last RL2.
- Plant physiology.Plant Physiol.2015 Nov;169(3):1821-35. doi: 10.1104/pp.15.00474. Epub 2015 May 18.
- PMID 25986128
- Diversification of Paralogous α-Isopropylmalate Synthases by Modulation of Feedback Control and Hetero-Oligomerization in Saccharomyces cerevisiae.
- López G1, Quezada H2, Duhne M2, González J2, Lezama M2, El-Hafidi M3, Colón M2, Martínez de la Escalera X2, Flores-Villegas MC2, Scazzocchio C4, DeLuna A5, González A2.
- Eukaryotic cell.Eukaryot Cell.2015 Jun;14(6):564-77. doi: 10.1128/EC.00033-15. Epub 2015 Apr 3.
- PMID 25841022
Related Links
- 2-isopropylmalate synthase (leuA) 3-isopropylmalate dehydratase small subunit (), 3-isopropylmalate dehydratase large subunit 3-isopropylmalate dehydrogenase Branched-chain-amino-acid aminotransferase View all proteins of . ...
- 2-isopropylmalate synthase 2, mitochondrial (), 2-isopropylmalate synthase (LEU4) 3-isopropylmalate dehydratase 3-isopropylmalate dehydrogenase Branched-chain-amino-acid aminotransferase, cytosolic (), Branched-chain) . i ...
- alpha-isopropylmalate synthase, isopropylmalate synthase, mtipms, alpha-ipms, alpha-isopropylmalate synthetase, alpha-ipm synthase, alpha-ipms-14cr, ipms2 ... nonrapid equilibrium bi-bi kinetic mechanism, with a preferred ...
★リンクテーブル★
[★]
- 英
- 2-isopropylmalate synthase
- 関
- 2-イソプロピルリンゴ酸シンターゼ
[★]
- 英
- 2-isopropylmalate synthase
- 関
- 2-イソプロピルリンゴ酸合成酵素
[★]
- 関
- lyase、synthetase、transferase