The structural basis for catalysis and substrate specificity of a rhomboid protease.

ABSTRACT: 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 S₁- and S₂'-binding subsites of GlpG, which are the key determinants of substrate specificity. The inhibitor-bound s

SUBMITTER: Vinothkumar KR 

PROVIDER: S-EPMC2989101 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature