6OW2

X-ray Structure of Polypeptide Deformylase

6OW2 の概要

• エントリーDOI: 10.2210/pdb6ow2/pdb
• 分子名称: Peptide deformylase, NICKEL (II) ION, (2R)-2-(cyclopentylmethyl)-N'-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methylpyrimidin-4-yl}-3-[hydroxy(hydroxymethyl)amino]propanehydrazide, ... (4 entities in total)
• 機能のキーワード: inhibitor, complex, metal protein, enzyme, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Streptococcus pneumoniae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23130.11

構造登録者

Campobasso, N.,Spletstoser, J.,Ward, P. (登録日: 2019-05-09, 公開日: 2019-06-26, 最終更新日: 2024-03-13)

主引用文献

Spletstoser, J.T.,Dreabit, J.,Knox, A.N.,Benowitz, A.,Campobasso, N.,Ward, P.,Cui, G.,Lewandowski, T.,McCloskey, L.,Aubart, K.M.
Discovery of piperazic acid peptide deformylase inhibitors with in vivo activity for respiratory tract and skin infections.
Bioorg.Med.Chem.Lett., 29:2410-2414, 2019

PubMed Abstract: The discovery of a novel series of peptide deformylase inhibitors incorporating a piperazic acid amino acid found in nature is described. These compounds demonstrated potent in vitro enzymatic potency and antimicrobial activity. Crystal structure analysis revealed the piperazic acid optimized a key contact with the PDF protein that accounted for the increased enzymatic potency of these compounds. We describe lead optimization of the P3' region of the series that resulted in a compound with good potency against three target organisms. One molecule showed in vivo efficacy in a rat respiratory infection model but ultimately did not meet candidate progression criteria.

PubMed: 31160176
DOI: 10.1016/j.bmcl.2019.05.028

実験手法

X-RAY DIFFRACTION (1.7 Å)