3asj

Crystal structure of homoisocitrate dehydrogenase in complex with a designed inhibitor

spinqualitylabelsall models 3asj, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3asj is a 4 chain structure with sequence from Thermus thermophilus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: MPD, XYM, XYN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HICDH_THET8 Catalyzes the NAD(+)-dependent oxidative decarboxylation of homoisocitrate to 2-oxoadipate (alpha-ketoadipate), a reaction involved in lysine biosynthesis through the alpha-aminoadipate pathway (PubMed:21813504). In addition, has high activity with isocitrate, but is inactive with 3-isopropylmalate (By similarity).[UniProtKB:Q72IW9] Publication Abstract from PubMed Homoisocitrate dehydrogenase (HICDH) is involved in the alpha-aminoadipate pathway of lysine biosynthesis in some bacteria and higher fungi, and catalyzes the oxidative decarboxylation of (2R,3S)-homoisocitrate into 2-ketoadipate using NAD(+) as a coenzyme. In this study, the crystal structure of Thermus thermophilus HICDH in a binary complex with a designed inhibitor, (2S,3S)-thiahomoisocitrate, has been determined at 2.6 A resolution. The inhibitor observed as a decarboxylated product interacts through hydrogen bonding to Arg 118, Tyr 125, and Lys 171 in the active site. The induced fitting was also observed around the region consisting of residues 120-141, which shifted up to 2.8 A toward the active site. In addition, it was found that the complex structure adopts a closed conformation in two domains. While the structure of apo-HICDH shows that a catalytic residue Tyr 125 and Arg 85 that engages in substrate recognition are flipped out of the active site, these residues turn toward the active site in the complex structure. The results revealed that they directly interact with a substrate and are involved in catalysis or substrate recognition. Furthermore, by comparing the binary complex with the quaternary complex of Escherichia coli isocitrate dehydrogenase, the substrate recognition mechanism of HICDH is also discussed. Structure of Thermus thermophilus Homoisocitrate Dehydrogenase in Complex with a Designed Inhibitor.,Nango E, Yamamoto T, Kumasaka T, Eguchi T J Biochem. 2011 Aug 3. PMID:21813504 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isocitrate dehydrogenase 3D structures

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