Structure of the diaminopimelate epimerase DapF from Mycobacterium tuberculosis

Usha, Veeraraghavan, Dover, Lynn, Roper, David, Futterer, Klaus and Besra, Gurdyal (2009) Structure of the diaminopimelate epimerase DapF from Mycobacterium tuberculosis. Acta Crystallographica, Section D: Biological Crystallography, 65 (4). pp. 383-387. ISSN 0907-4449

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Official URL: http://dx.doi.org/10.1107/S0907444909002522

Abstract

The meso (or D,L) isomer of diaminopimelic acid (DAP), a precursor of L-lysine, is a key component of the pentapeptide linker in bacterial peptidoglycan. While the peptidoglycan incorporated in the highly complex cell wall of the pathogen Mycobacterium tuberculosis structurally resembles that of Escherichia coli, it is unique in that it can contain penicillin-resistant meso-DAPmeso-DAP linkages. The interconversion of L,L-DAP and meso-DAP is catalysed by the DAP epimerase DapF, a gene product that is essential in M. tuberculosis. Here, the crystal structure of the ligand-free form of M. tuberculosis DapF (MtDapF) refined to a resolution of 2.6 Å is reported. MtDapF shows small if distinct deviations in secondary structure from the two-domain /-fold of the known structures of Haemophilus influenzae DapF and Bacillus anthracis DapF, which are in line with its low sequence identity (27%) to the former. Modelling the present structure onto that of L,L-aziridino-DAP-bound H. influenzae DapF illustrates that a rigid-body movement of domain II and a rearrangement of the B4-A2 loop (residues 80-90) of domain I are likely to accompany the transition from the present inactive form to a catalytically competent enzyme. Despite a highly conserved active-site architecture, the model indicates that stabilization of the DAP backbone occurs in MtDapF through a tyrosine residue that is specific to mycobacterial DAP epimerases.

Item Type: Article
Uncontrolled Keywords: diaminopimelate epimerase, mycobacterium tuberculosis
Subjects: C100 Biology
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: EPrints Services
Date Deposited: 11 May 2010 08:34
Last Modified: 10 Aug 2015 11:45
URI: http://nrl.northumbria.ac.uk/id/eprint/707

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