2xow

Structure of GlpG in complex with a mechanism-based isocoumarin inhibitor

spinqualitylabelsall models 2xow, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xow is a 1 chain structure with sequence from Escherichia coli. The August 2011 RCSB PDB Molecule of the Month feature on Rhomboid Protease GlpG by David Goodsell is 10.2210/rcsb_pdb/mom_2011_8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.09Å Ligands: BNG, ISM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLPG_ECOLI Rhomboid-type serine protease that catalyzes intramembrane proteolysis. Publication Abstract from PubMed Rhomboids are intramembrane proteases that use a catalytic dyad of serine and histidine for proteolysis. They are conserved in both prokaryotes and eukaryotes and regulate cellular processes as diverse as intercellular signalling, parasitic invasion of host cells, and mitochondrial morphology. Their widespread biological significance and consequent medical potential provides a strong incentive to understand the mechanism of these unusual enzymes for identification of specific inhibitors. In this study, we describe the structure of Escherichia coli rhomboid GlpG covalently bound to a mechanism-based isocoumarin inhibitor. We identify the position of the oxyanion hole, and the S(1)- and S(2)'-binding subsites of GlpG, which are the key determinants of substrate specificity. The inhibitor-bound structure suggests that subtle structural change is sufficient for catalysis, as opposed to large changes proposed from previous structures of unliganded GlpG. Using bound inhibitor as a template, we present a model for substrate binding at the active site and biochemically test its validity. This study provides a foundation for a structural explanation of rhomboid specificity and mechanism, and for inhibitor design. The structural basis for catalysis and substrate specificity of a rhomboid protease.,Vinothkumar KR, Strisovsky K, Andreeva A, Christova Y, Verhelst S, Freeman M EMBO J. 2010 Oct 1. PMID:20890268 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Rhomboid protease

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