6QBU

Crystal structure of Porcine Pancreatic Elastase (PPE) in complex with the 3-Oxo-beta-Sultam inhibitor LMC188

6QBU の概要

• エントリーDOI: 10.2210/pdb6qbu/pdb
• 分子名称: Chymotrypsin-like elastase family member 1, ~{N}-[[1-[(4-chlorophenyl)methyl]-1,2,3-triazol-4-yl]methyl]-2-hydrosulfonyl-2-methyl-propanamide, PHOSPHATE ION, ... (6 entities in total)
• 機能のキーワード: serine hydrolases, pancreatic porcine elastase, inhibitor, 3-oxo-beta-sultams, sulfonylation, hydrolase
• 由来する生物種: Sus scrofa (Pig)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26616.95

構造登録者

Brito, J.A.,Almeida, V.T.,Carvalho, L.M.,Moreira, R.,Archer, M. (登録日: 2018-12-21, 公開日: 2020-04-08, 最終更新日: 2024-10-23)

主引用文献

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

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: 32176480
DOI: 10.1021/acschembio.0c00090

実験手法

X-RAY DIFFRACTION (1.38 Å)