Structural highlights
FunctionGLPG_ECOLI Rhomboid-type serine protease that catalyzes intramembrane proteolysis.[1] [2] Publication Abstract from PubMedRhomboid proteases are evolutionary conserved intramembrane serine proteases. Because of their emerging role in many important biological pathways, rhomboids are potential drug targets. Unfortunately, few chemical tools are available for their study. Here, we describe a mass spectrometry-based assay to measure rhomboid substrate cleavage and inhibition. We have identified isocoumarin inhibitors and developed activity-based probes for rhomboid proteases. The probes can distinguish between active and inactive rhomboids due to covalent, reversible binding of the active-site serine and stable modification of a histidine residue. Finally, the structure of an isocoumarin-based inhibitor with Escherichia coli rhomboid GlpG uncovers an unusual mode of binding at the active site and suggests that the interactions between the 3-substituent on the isocoumarin inhibitor and hydrophobic residues on the protease reflect S' subsite binding. Overall, these probes represent valuable tools for rhomboid study, and the structural insights may facilitate future inhibitor design. Activity-based probes for rhomboid proteases discovered in a mass spectrometry-based assay.,Vosyka O, Vinothkumar KR, Wolf EV, Brouwer AJ, Liskamp RM, Verhelst SH Proc Natl Acad Sci U S A. 2013 Jan 28. PMID:23359682[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
This page was last modified 11:00, 20 December 2023.