5DQL

Crystal Structure of 2-vinyl glyoxylate modified isocitrate lyase from Mycobacterium tuberculosis

5DQL の概要

• エントリーDOI: 10.2210/pdb5dql/pdb
• 分子名称: Isocitrate lyase 1, MAGNESIUM ION, 4-hydroxy-2-oxobutanoic acid, ... (4 entities in total)
• 機能のキーワード: lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 189131.44

構造登録者

Huang, H.-L.,Meek, T.D. (登録日: 2015-09-14, 公開日: 2016-09-14, 最終更新日: 2024-10-23)

主引用文献

Pham, T.V.,Murkin, A.S.,Moynihan, M.M.,Harris, L.,Tyler, P.C.,Shetty, N.,Sacchettini, J.C.,Huang, H.L.,Meek, T.D.
Mechanism-based inactivator of isocitrate lyases 1 and 2 from Mycobacterium tuberculosis.
Proc. Natl. Acad. Sci. U.S.A., 114:7617-7622, 2017

PubMed Abstract: Isocitrate lyase (ICL, types 1 and 2) is the first enzyme of the glyoxylate shunt, an essential pathway for () during the persistent phase of human TB infection. Here, we report 2-vinyl-d-isocitrate (2-VIC) as a mechanism-based inactivator of ICL1 and ICL2. The enzyme-catalyzed retro-aldol cleavage of 2-VIC unmasks a Michael substrate, 2-vinylglyoxylate, which then forms a slowly reversible, covalent adduct with the thiolate form of active-site Cys 2-VIC displayed kinetic properties consistent with covalent, mechanism-based inactivation of ICL1 and ICL2 with high efficiency (partition ratio, <1). Analysis of a complex of ICL1:2-VIC by electrospray ionization mass spectrometry and X-ray crystallography confirmed the formation of the predicted covalent -homopyruvoyl adduct of the active-site Cys.

PubMed: 28679637
DOI: 10.1073/pnas.1706134114

実験手法

X-RAY DIFFRACTION (1.782 Å)