PDBsum entry 3log

Isomerase

PDB id: 3log

Contents

Protein chains

435 a.a. *

Ligands

SIN ×5

GOL ×5

CO3

Metals

_NA

Waters ×1624

* Residue conservation analysis

PDB id:

3log

Name:

Isomerase

Title:

Crystal structure of mbti from mycobacterium tuberculosis

Structure:

Isochorismate synthase/isochorismate-pyruvate lyase mbti. Chain: a, b, c, d. Synonym: salicylate synthase mbti, mycobactin synthetase protein i. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: mbti, mt2454, rv2386c. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.73Å R-factor: 0.183 R-free: 0.225

Authors:

E.M.M.Bulloch,J.S.Lott,E.N.Baker,J.M.Johnston

Key ref:

A.Manos-Turvey et al. (2010). Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI). Chemmedchem, 5, 1067-1079. PubMed id: 20512795

Date:

03-Feb-10 Release date: 09-Feb-11

Protein chains

P9WFX1  (MBTI_MYCTU) -  Salicylate synthase from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 450 a.a.

Struc: 435 a.a.

Enzyme reactions

• Enzyme class 1: E.C.4.2.99.21 - isochorismate lyase.
• Reaction: isochorismate = salicylate + pyruvate

isochorismate = salicylate (Bound ligand (Het Group name = SIN) matches with 55.56% similarity) + pyruvate

• Enzyme class 2: E.C.5.4.4.2 - isochorismate synthase.

Pathway:

• Reaction: chorismate = isochorismate

chorismate (Bound ligand (Het Group name = SIN) matches with 41.18% similarity) = isochorismate

• Cofactor: Mg(2+)
• Enzyme class 3: E.C.5.4.99.5 - chorismate mutase.

Pathway:

• Reaction: chorismate = prephenate

chorismate (Bound ligand (Het Group name = SIN) matches with 41.18% similarity) = prephenate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Chemmedchem 5:1067-1079 (2010)

PubMed id: 20512795

Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI).

A.Manos-Turvey, E.M.Bulloch, P.J.Rutledge, E.N.Baker, J.S.Lott, R.J.Payne.

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.