3ivs | pdb_00003ivs

Homocitrate Synthase Lys4

spinqualitylabelsall models 3ivs, resolution 2.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ivs is a 2 chain structure with sequence from Cbs 356. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CO, MG NonStd Res: MSE Related: 3ivt, 3ivu Gene: lys4, SPBC1105.02c (CBS 356) Activity: Homocitrate synthase, with EC number 2.3.3.14 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 Homocitrate synthase (HCS) catalyzes the first and committed step in lysine biosynthesis in many fungi and certain Archaea and is a potential target for antifungal drugs. Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). The structures reveal that HCS forms an intertwined homodimer stabilized by domain-swapping between the N- and C-terminal domains of each monomer. The N-terminal catalytic domain is composed of a TIM barrel fold in which 2-OG binds via hydrogen bonds and coordination to the active site divalent metal ion, whereas the C-terminal domain is composed of mixed alpha/beta topology. In the structures of the HCS apoenzyme and one of the 2-OG binary complexes, a lid motif from the C-terminal domain occludes the entrance to the active site of the neighboring monomer, whereas in the second 2-OG complex the lid is disordered, suggesting that it regulates substrate access to the active site through its apparent flexibility. Mutations of the active site residues involved in 2-OG binding or implicated in acid-base catalysis impair or abolish activity in vitro and in vivo. Together, these results yield new insights into the structure and catalytic mechanism of HCSs and furnish a platform for developing HCS-selective inhibitors. Crystal structure and functional analysis of homocitrate synthase, an essential enzyme in lysine biosynthesis.,Bulfer SL, Scott EM, Couture JF, Pillus L, Trievel RC J Biol Chem. 2009 Dec 18;284(51):35769-80. Epub . PMID:19776021 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Homocitrate synthase

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