3LOG: Crystal structure of MbtI from Mycobacterium tuberculosis

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.
PDB ID: 3LOGDownload
MMDB ID: 88480
PDB Deposition Date: 2010/2/3
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.73  Å
Source Organism:
Similar Structures:
Biological Unit for 3LOG: monomeric; determined by author and by software (PISA)
Molecular Components in 3LOG
Label Count Molecule
Protein (1 molecule)
Isochorismate Synthase/isochorismate-pyruvate Lyase Mbti
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB