Structural highlights
3log is a 4 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Gene: | mbtI, MT2454, Rv2386c ("Bacillus tuberculosis" (Zopf 1883) Klein 1884) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[MBTI_MYCTU] Mediates the production of salicylate from chorismate via an isochorismate intermediate. Presents both isochorismate synthase and isochorismate-pyruvate lyase activities. Salycilate is the starter unit in the production of the virulence-conferring salicylate-based siderophore mycobactin.[1]
Publication Abstract from PubMed
Mycobacterium tuberculosis salicylate synthase (MbtI), a member of the chorismate-utilizing enzyme family, catalyses the first committed step in the biosynthesis of the siderophore mycobactin T. This complex secondary metabolite is essential for both virulence and survival of M. tuberculosis, the etiological agent of tuberculosis (TB). It is therefore anticipated that inhibitors of this enzyme may serve as TB therapies with a novel mode of action. Herein we describe the first inhibition study of M. tuberculosis MbtI using a library of functionalized benzoate-based inhibitors designed to mimic the substrate (chorismate) and intermediate (isochorismate) of the MbtI-catalyzed reaction. The most potent inhibitors prepared were those designed to mimic the enzyme intermediate, isochorismate. These compounds, based on a 2,3-dihydroxybenzoate scaffold, proved to be low-micromolar inhibitors of MbtI. The most potent inhibitors in this series possessed hydrophobic enol ether side chains at C3 in place of the enol-pyruvyl side chain found in chorismate and isochorismate.
Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI).,Manos-Turvey A, Bulloch EM, Rutledge PJ, Baker EN, Lott JS, Payne RJ ChemMedChem. 2010 Jul 5;5(7):1067-79. PMID:20512795[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Harrison AJ, Yu M, Gardenborg T, Middleditch M, Ramsay RJ, Baker EN, Lott JS. The structure of MbtI from Mycobacterium tuberculosis, the first enzyme in the biosynthesis of the siderophore mycobactin, reveals it to be a salicylate synthase. J Bacteriol. 2006 Sep;188(17):6081-91. PMID:16923875 doi:http://dx.doi.org/188/17/6081
- ↑ Manos-Turvey A, Bulloch EM, Rutledge PJ, Baker EN, Lott JS, Payne RJ. Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI). ChemMedChem. 2010 Jul 5;5(7):1067-79. PMID:20512795 doi:10.1002/cmdc.201000137
