3LOG

Crystal structure of MbtI from Mycobacterium tuberculosis

Summary for 3LOG

• Entry DOI: 10.2210/pdb3log/pdb
• Descriptor: Isochorismate synthase/isochorismate-pyruvate lyase mbtI, SUCCINIC ACID, GLYCEROL, ... (6 entities in total)
• Functional Keywords: chorismate, salicylate, anthranilate, isochorismate, isochorismate synthase, isochorismate lyase, ion transport, isomerase, lyase, metal-binding, multifunctional enzyme, transport
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 4
• Total formula weight: 196442.86

Authors

Bulloch, E.M.M.,Lott, J.S.,Baker, E.N.,Johnston, J.M. (deposition date: 2010-02-03, release date: 2011-02-09, Last modification date: 2023-11-01)

Primary citation

Manos-Turvey, A.,Bulloch, E.M.,Rutledge, P.J.,Baker, E.N.,Lott, J.S.,Payne, R.J.
Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI).
Chemmedchem, 5:1067-1079, 2010

PubMed Abstract: 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.

PubMed: 20512795
DOI: 10.1002/cmdc.201000137

Experimental method

X-RAY DIFFRACTION (1.73 Å)