2b7o

From Proteopedia

The Structure of 3-Deoxy-D-Arabino-Heptulosonate 7-Phosphate Synthase from Mycobacterium tuberculosis

Overview

The shikimate pathway, responsible for the biosynthesis of aromatic, compounds, is essential for the growth of Mycobacterium tuberculosis and, is a potential target for the design of new anti-tuberculosis drugs. The, first step of this pathway is catalyzed by 3-deoxy-d-arabino-heptulosonate, 7-phosphate synthase (DAH7PS). The DAH7PSs have been classified into two, apparently unrelated types and, whereas structural data have been obtained, for the type I DAH7PSs, no structural information is available for their, type II counterparts. The type II DAH7PS from M.tuberculosis has been, expressed in Escherichia coli, purified, functionally characterized and, crystallized. It is found to be metal ion-dependent and subject to, feedback inhibition by phenylalanine, tryptophan, tyrosine and chorismate, with a significant synergistic effect when tryptophan is used in, combination with phenylalanine. The crystal structure of M.tuberculosis, DAH7PS has been determined by single-wavelength anomalous diffraction and, refined at 2.3A in complex with substrate phosphoenolpyruvate and Mn(2+)., The structure reveals a tightly associated dimer of (beta/alpha)(8) TIM, barrels. The monomer fold, the arrangement of key residues in the active, site, and the binding modes of PEP and Mn(2+), all match those of the type, I enzymes, and indicate a common ancestry for the type I and type II, DAH7PSs, despite their minimal sequence identity. In contrast, the, structural elements that decorate the core (beta/alpha)(8) fold differ, from those in the type I enzymes, consistent with their different, regulatory and oligomeric properties.

About this Structure

2B7O is a Single protein structure of sequence from Mycobacterium tuberculosis with , , and as ligands. Full crystallographic information is available from OCA.

Reference

The structure of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis reveals a common catalytic scaffold and ancestry for type I and type II enzymes., Webby CJ, Baker HM, Lott JS, Baker EN, Parker EJ, J Mol Biol. 2005 Dec 9;354(4):927-39. Epub 2005 Oct 21. PMID:16288916

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