3ZEB
A complex of GlpG with isocoumarin inhibitor covalently bonded to serine 201 and histidine 150
Summary for 3ZEB
| Entry DOI | 10.2210/pdb3zeb/pdb |
| Descriptor | RHOMBOID PROTEASE GLPG, 2-phenylethyl 2-(4-azanyl-2-methanoyl-phenyl)ethanoate, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | hydrolase, intra-membrane protease, serine protease, acyl enzyme |
| Biological source | ESCHERICHIA COLI |
| Total number of polymer chains | 1 |
| Total formula weight | 22064.77 |
| Authors | Vinothkumar, K.R.,voskya, O.,Kuettler, E.V.,Brouwer, A.J.,Liskamp, R.M.J.,Verhelst, S.H.L. (deposition date: 2012-12-04, release date: 2013-02-13, Last modification date: 2024-11-13) |
| Primary citation | Vosyka, O.,Vinothkumar, K.R.,Wolf, E.V.,Brouwer, A.J.,Liskamp, R.M.J.,Verhelst, S.H.L. Activity-Based Probes for Rhomboid Proteases Discovered in a Mass Spectrometry-Based Assay. Proc.Natl.Acad.Sci.USA, 110:2472-, 2013 Cited by PubMed Abstract: Rhomboid 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. PubMed: 23359682DOI: 10.1073/PNAS.1215076110 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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