Structure of the Diaminopimelate Epimerase DapF From Mycobacterium Tuberculosis

Acta Crystallogr D Biol Crystallogr. 2009 Apr;65(Pt 4):383-7. doi: 10.1107/S0907444909002522. Epub 2009 Mar 19.

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-DAP-->meso-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 A is reported. MtDapF shows small if distinct deviations in secondary structure from the two-domain alpha/beta-fold of the known structures of Haemophilus influenzae DapF and Bacillus anthracis DapF, which are in line with its low sequence identity (<or=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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Isomerases / chemistry*
  • Bacillus anthracis / enzymology
  • Bacterial Proteins / chemistry*
  • Catalytic Domain
  • Crystallography, X-Ray
  • Haemophilus influenzae / enzymology
  • Models, Chemical
  • Models, Molecular
  • Mycobacterium tuberculosis / enzymology*
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Species Specificity

Substances

  • Bacterial Proteins
  • Amino Acid Isomerases
  • diaminopimelate epimerase