9B96

Crystal structure of the human PAD2 protein bound to inhibitor

これはPDB形式変換不可エントリーです。

9B96 の概要

• エントリーDOI: 10.2210/pdb9b96/pdb
• 分子名称: Protein-arginine deiminase type-2, 1-({(2P)-1-{(1R)-1-(2-bromophenyl)-3-[5-(methanesulfonamido)-2-methylanilino]-3-oxopropyl}-2-[3-(4-chlorophenoxy)phenyl]-1H-1,3-benzimidazol-6-yl}methyl)-N-methyl-D-prolinamide, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: inhibitor, complex, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 79821.66

構造登録者

Byrnes, L.J.,Vajdos, F. (登録日: 2024-04-01, 公開日: 2024-10-09, 最終更新日: 2024-10-30)

主引用文献

Byrnes, L.J.,Choi, W.Y.,Balbo, P.,Banker, M.E.,Chang, J.,Chen, S.,Cheng, X.,Cong, Y.,Culp, J.,Di, H.,Griffor, M.,Hall, J.,Meng, X.,Morgan, B.,Mousseau, J.J.,Nicki, J.,O'Connell, T.,Ramsey, S.,Shaginian, A.,Shanker, S.,Trujillo, J.,Wan, J.,Vincent, F.,Wright, S.W.,Vajdos, F.
Discovery, Characterization, and Structure of a Cell Active PAD2 Inhibitor Acting through a Novel Allosteric Mechanism.
Acs Chem.Biol., 19:2186-2197, 2024

PubMed Abstract: Peptidyl arginine deiminases (PADs) are important enzymes in many diseases, especially those involving inflammation and autoimmunity. Despite many years of effort, developing isoform-specific inhibitors has been a challenge. We describe herein the discovery of a potent, noncovalent PAD2 inhibitor, with selectivity over PAD3 and PAD4, from a DNA-encoded library. The biochemical and biophysical characterization of this inhibitor and two noninhibitory binders indicated a novel, Ca competitive mechanism of inhibition. This was confirmed via X-ray crystallographic analysis. Finally, we demonstrate that this inhibitor selectively inhibits PAD2 in a cellular context.

PubMed: 39316753
DOI: 10.1021/acschembio.4c00397

実験手法

X-RAY DIFFRACTION (1.64 Å)