6QEO
Crystal structure of Porcine Pancreatic Elastase (PPE) in complex with the 3-Oxo-beta-Sultam inhibitor LMC269
Summary for 6QEO
| Entry DOI | 10.2210/pdb6qeo/pdb |
| Related | 6QBU 6QEN |
| Descriptor | Chymotrypsin-like elastase family member 1, 2-methyl-1-[[1-[(4-nitrophenyl)methyl]-1,2,3-triazol-4-yl]methylamino]-1-oxidanylidene-propane-2-sulfonic acid, PHOSPHATE ION, ... (6 entities in total) |
| Functional Keywords | serine hydrolases, pancreatic porcine elastase, inhibitor, 3-oxo-beta-sultams, sulfonylation, hydrolase |
| Biological source | Sus scrofa (Pig) |
| Total number of polymer chains | 1 |
| Total formula weight | 26643.50 |
| Authors | Brito, J.A.,Almeida, V.T.,Carvalho, L.M.,Moreira, R.,Archer, M. (deposition date: 2019-01-08, release date: 2020-04-08, Last modification date: 2024-11-20) |
| Primary citation | Carvalho, L.A.R.,Almeida, V.T.,Brito, J.A.,Lum, K.M.,Oliveira, T.F.,Guedes, R.C.,Goncalves, L.M.,Lucas, S.D.,Cravatt, B.F.,Archer, M.,Moreira, R. 3-Oxo-beta-sultam as a Sulfonylating Chemotype for Inhibition of Serine Hydrolases and Activity-Based Protein Profiling. Acs Chem.Biol., 15:878-883, 2020 Cited by PubMed Abstract: 3-Oxo-β-sultams are four-membered ring ambident electrophiles that can react with nucleophiles either at the carbonyl carbon or at the sulfonyl sulfur atoms, and that have been reported to inhibit serine hydrolases via acylation of the active-site serine residue. We have developed a panel of 3-oxo-β-sultam inhibitors and show, through crystallographic data, that they are regioselective sulfonylating electrophiles, covalently binding to the catalytic serine of human and porcine elastases through the sulfur atom. Application of 3-oxo-β-sultam-derived activity-based probes in a human proteome revealed their potential to label disease-related serine hydrolases and proteasome subunits. Activity-based protein profiling applications of 3-oxo-β-sultams should open up new opportunities to investigate these classes of enzymes in complex proteomes and expand the toolbox of available sulfur-based covalent protein modifiers in chemical biology. PubMed: 32176480DOI: 10.1021/acschembio.0c00090 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3 Å) |
Structure validation
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