3HRH

Crystal Structure of Antigen 85C and Glycerol

3HRH の概要

• エントリーDOI: 10.2210/pdb3hrh/pdb
• 関連するPDBエントリー: 1DQY 1DQZ 1SFR 1f0n 1f0p 1va5
• 分子名称: Antigen 85-C, GLYCEROL (3 entities in total)
• 機能のキーワード: alpha/beta hydrolase, acyltransferase, secreted, hydrolase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68327.45

構造登録者

Boucau, J.,Sanki, A.K.,Umesiri, F.E.,Sucheck, S.J.,Ronning, D.R. (登録日: 2009-06-09, 公開日: 2009-09-29, 最終更新日: 2023-09-06)

主引用文献

Sanki, A.K.,Boucau, J.,Umesiri, F.E.,Ronning, D.R.,Sucheck, S.J.
Design, synthesis and biological evaluation of sugar-derived esters, alpha-ketoesters and alpha-ketoamides as inhibitors for Mycobacterium tuberculosis antigen 85C.
Mol Biosyst, 5:945-956, 2009

PubMed Abstract: Peptide-based 1,2-dicarbonyl compounds have emerged as potent inhibitors for serine proteases. Herein, we have designed and synthesized d-arabinose and d-trehalose-based esters, alpha-ketoesters and alpha-ketoamides, and evaluated their inhibitory activity against Mycobacterium tuberculosis (Mtb) antigen 85C (ag85C), an acyltransferase in the serine hydrolase superfamily. In addition the compounds were evaluated for the ability to inhibit the growth of Mycobacterium smegmatis ATCC 14 468, a non-pathogenic surrogate for Mtb. Among the synthetic analogs evaluated only the methyl ester derived from d-arabinose was found to inhibit the acyltransferase activity of ag85C (IC(50) = 25 mM). Based on this weak inhibitory activity it was not surprising that none of the compounds inhibits the growth of M. smegmatis. In spite of the weak inhibitory activity of , X-ray crystallography on crystals of ag85C soaked with suggested the formation of a covalent ester adduct between and the Ser124 side chain hydroxyl moiety found within the catalytic site of ag85C; however, some of the active site electron density appears to result from bound glycerol. The lack of activity associated with the alpha-ketoester and alpha-ketoamide derivatives of d-trehalose may be the result of intramolecular cyclization of the alpha-keto moiety with the nearby C-4/4' hydroxyls leading to the formation of stable bicyclo-ester and amide derivatives.

PubMed: 19668859
DOI: 10.1039/b902284h

実験手法

X-RAY DIFFRACTION (2.3 Å)