2ztw | pdb_00002ztw

Structure of 3-isopropylmalate dehydrogenase in complex with the inhibitor and NAD+

spinqualitylabelsall models 2ztw, resolution 2.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ztw is a 1 chain structure with sequence from Thermus thermophilus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DEI, MG, NAD Gene: leuB, TTHA1230 (Thermus thermophilus) Activity: 3-isopropylmalate dehydrogenase, with EC number 1.1.1.85 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Isopropylmalate dehydrogenase (IPMDH) is the third enzyme specific to leucine biosynthesis in microorganisms and plants, and catalyzes the oxidative decarboxylation of (2R,3S)-3-isopropylmalate to alpha-ketoisocaproate using NAD(+) as an oxidizing agent. In this study, a thia-analogue of the substrate was designed and synthesized as an inhibitor for IPMDH. The analogue showed strong competitive inhibitory activity with K(i)=62nM toward IPMDH derived from Thermus thermophilus. Moreover, the crystal structure of T. thermophilus IPMDH in a ternary complex with NAD(+) and the inhibitor has been determined at 2.8A resolution. The inhibitor exists as a decarboxylated product with an enol/enolate form in the active site. The product interacts with Arg 94, Asn 102, Ser 259, Glu 270, and a water molecule hydrogen-bonding with Arg 132. All interactions between the product and the enzyme were observed in the position associated with keto-enol tautomerization. This result implies that the tautomerization step of the thia-analogue during the IPMDH reaction is involved in the inhibition. Crystal structure of 3-isopropylmalate dehydrogenase in complex with NAD(+) and a designed inhibitor.,Nango E, Yamamoto T, Kumasaka T, Eguchi T Bioorg Med Chem. 2009 Nov 15;17(22):7789-94. Epub 2009 Sep 19. PMID:19833522 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isopropylmalate dehydrogenase

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