3mi3

Homocitrate Synthase Lys4 bound to LysineHomocitrate Synthase Lys4 bound to Lysine

Structural highlights 3mi3 is a 2 chain structure with sequence from Schizosaccharomyces pombe. This structure supersedes the now removed PDB entry 3l90. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.38Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HOSM_SCHPO 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 The alpha-aminoadipate pathway of lysine biosynthesis is modulated at the transcriptional and biochemical levels by feedback inhibition. The first enzyme in the alpha-aminoadipate pathway, homocitrate synthase (HCS), is the target of the feedback regulation and is strongly inhibited by l-lysine. Here we report the structure of Schizosaccharomyces pombe HCS (SpHCS) in complex with l-lysine. The structure illustrates that the amino acid directly competes with the substrate 2-oxoglutarate for binding within the active site of HCS. Differential recognition of the substrate and inhibitor is achieved via a switch position within the (alpha/beta)(8) TIM barrel of the enzyme that can distinguish between the C5-carboxylate group of 2-oxoglutarate and the epsilon-ammonium group of l-lysine. In vitro and in vivo assays demonstrate that mutations of the switch residues, which interact with the l-lysine epsilon-ammonium group, abrogate feedback inhibition, as do substitutions of residues within the C-terminal domain that were identified in a previous study of l-lysine-insensitive HCS mutants in Saccharomyces cerevisiae. Together, these results yield new insights into the mechanism of feedback regulation of an enzyme central to lysine biosynthesis. Structural basis for L-lysine feedback inhibition of homocitrate synthase.,Bulfer SL, Scott EM, Pillus L, Trievel RC J Biol Chem. 2010 Apr 2;285(14):10446-53. Epub 2010 Jan 19. PMID:20089861 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Homocitrate synthase

spinqualitylabelsall models 3mi3, resolution 2.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image