5DQL
Crystal Structure of 2-vinyl glyoxylate modified isocitrate lyase from Mycobacterium tuberculosis
Summary for 5DQL
| Entry DOI | 10.2210/pdb5dql/pdb |
| Descriptor | Isocitrate lyase 1, MAGNESIUM ION, 4-hydroxy-2-oxobutanoic acid, ... (4 entities in total) |
| Functional Keywords | lyase-lyase inhibitor complex, lyase/lyase inhibitor |
| Biological source | Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman) |
| Total number of polymer chains | 4 |
| Total formula weight | 189131.44 |
| Authors | Huang, H.-L.,Meek, T.D. (deposition date: 2015-09-14, release date: 2016-09-14, Last modification date: 2024-10-23) |
| Primary citation | 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 Cited by 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: 28679637DOI: 10.1073/pnas.1706134114 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.782 Å) |
Structure validation
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