Structural highlights
Function
INLPD_MYCTU Involved in the biosynthesis of a unique class of isonitrile lipopeptides (INLPs) that seem to function as virulence factors in M.tuberculosis and to play a role in metal acquisition (PubMed:28634299). Catalyzes a Michael addition of glycine to the beta-position of an alpha,beta-unsaturated fatty acyl-[ACP], producing a (3R)-3-[(carboxymethyl)amino]fatty acid. Acts on the (2E)-decenoyl moiety loaded on the acyl-carrier protein (ACP) Rv0100, forming the product (3R)-3-[(carboxymethyl)amino]decanoate released from the ACP (By similarity). Displays thioesterase activity with a preference for long chain fatty acyl groups; in vitro, cleaves the thioester linkage of palmitoyl-CoA, stearoyl-CoA, lauroyl-CoA and hexanoyl-CoA (PubMed:17524985). Contains low levels of trans-enoyl hydratase activity (PubMed:19136596).[UniProtKB:B2HKM2][1] [2] [3]
Publication Abstract from PubMed
Rv0098 is part of an operon, Rv0096-Rv0101, from Mycobacterium tuberculosis (Mtb) that is essential for Mtb's survival in mouse macrophages. This operon also contains an acyl carrier protein and one of the only two nonribosomal peptide synthases in Mtb. Rv0098 is annotated in the genome as a hypothetical protein and was proposed to be an acyl-coenzyme A (CoA) dehydratase. The structure of Rv0098, together with subsequent biochemical analysis, indicated that Rv0098 is a long-chain fatty acyl-CoA thioesterase (FcoT). However, FcoT lacks a general base or a nucleophile that is always found in the catalytic site of type II and type I thioesterases, respectively. The active site of Mtb FcoT reveals the structural basis for its substrate specificity for long-chain acyl-CoA and allows us to propose a catalytic mechanism for the enzyme. The characterization of Mtb FcoT provides a putative function of this operon that is crucial for Mtb pathogenicity.
Identification of a type III thioesterase reveals the function of an operon crucial for Mtb virulence.,Wang F, Langley R, Gulten G, Wang L, Sacchettini JC Chem Biol. 2007 May;14(5):543-51. PMID:17524985[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang F, Langley R, Gulten G, Wang L, Sacchettini JC. Identification of a type III thioesterase reveals the function of an operon crucial for Mtb virulence. Chem Biol. 2007 May;14(5):543-51. PMID:17524985 doi:http://dx.doi.org/S1074-5521(07)00141-X
- ↑ Gurvitz A, Hiltunen JK, Kastaniotis AJ. Heterologous expression of mycobacterial proteins in Saccharomyces cerevisiae reveals two physiologically functional 3-hydroxyacyl-thioester dehydratases, HtdX and HtdY, in addition to HadABC and HtdZ. J Bacteriol. 2009 Apr;191(8):2683-90. doi: 10.1128/JB.01046-08. Epub 2009 Jan 9. PMID:19136596 doi:http://dx.doi.org/10.1128/JB.01046-08
- ↑ Harris NC, Sato M, Herman NA, Twigg F, Cai W, Liu J, Zhu X, Downey J, Khalaf R, Martin J, Koshino H, Zhang W. Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7025-7030. PMID:28634299 doi:10.1073/pnas.1705016114
- ↑ Wang F, Langley R, Gulten G, Wang L, Sacchettini JC. Identification of a type III thioesterase reveals the function of an operon crucial for Mtb virulence. Chem Biol. 2007 May;14(5):543-51. PMID:17524985 doi:http://dx.doi.org/S1074-5521(07)00141-X
