Structural highlights
Function
ACEA_MYCTU Catalyzes the formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle. May be involved in the assimilation of one-carbon compounds via the isocitrate lyase-positive serine pathway (By similarity).
Publication Abstract from PubMed
Isocitrate lyase (ICL, types 1 and 2) is the first enzyme of the glyoxylate shunt, an essential pathway for Mycobacterium tuberculosis (Mtb) during the persistent phase of human TB infection. Here, we report 2-vinyl-d-isocitrate (2-VIC) as a mechanism-based inactivator of Mtb 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 Cys191 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 S-homopyruvoyl adduct of the active-site Cys191.
Mechanism-based inactivator of isocitrate lyases 1 and 2 from Mycobacterium tuberculosis.,Pham TV, Murkin AS, Moynihan MM, Harris L, Tyler PC, Shetty N, Sacchettini JC, Huang HL, Meek TD Proc Natl Acad Sci U S A. 2017 Jul 18;114(29):7617-7622. doi:, 10.1073/pnas.1706134114. Epub 2017 Jul 5. PMID:28679637[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pham TV, Murkin AS, Moynihan MM, Harris L, Tyler PC, Shetty N, Sacchettini JC, Huang HL, Meek TD. Mechanism-based inactivator of isocitrate lyases 1 and 2 from Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2017 Jul 18;114(29):7617-7622. doi:, 10.1073/pnas.1706134114. Epub 2017 Jul 5. PMID:28679637 doi:http://dx.doi.org/10.1073/pnas.1706134114
