Structural and biochemical characterization of Rv2140c, a phosphatidylethanolamine-binding protein from Mycobacterium tuberculosis

• Published in: FEBS letters 2013-09, Vol.587 (18), p.2936-2942
• Main Authors: Eulenburg, Georg, Higman, Victoria A., Diehl, Anne, Wilmanns, Matthias, Holton, Simon J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding Sites; conserved region; Conserved Sequence; Crystallography, X-Ray; DHPE; DHPG; DHPS; dihexanoyl phosphatidylethanolamine; dihexanoyl phosphatidylglycerol; dihexanoyl phosphatidylserine; isothermal titration calorimetry; ITC; Ligands; Lipid Metabolism; Models, Molecular; Molecular Sequence Data; Mycobacterium smegmatis; Mycobacterium smegmatis - drug effects; Mycobacterium smegmatis - genetics; Mycobacterium smegmatis - metabolism; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; Oxazolidinones - chemistry; Oxazolidinones - pharmacology; PEBP; phosphatidylethanolamine; Phosphatidylethanolamine Binding Protein - chemistry; Phosphatidylethanolamine Binding Protein - genetics; Phosphatidylethanolamine Binding Protein - metabolism; phosphatidylethanolamine-binding protein; Phosphatidylethanolamines - chemistry; Phosphatidylethanolamines - metabolism; Protein Binding; Protein Multimerization; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Structural biology; Tuberculosis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2013.07.038

•Novel X-ray structures of the Mtb Rv2140c protein in apo and sulfate-bound forms.•Rv2140c has strong structural homology to the phosphatidylethanolamine-binding protein family.•Rv2140c forms low-millimolar interactions with soluble phosphatidylethanolamine analogs.•The small molecule locostatin binds to the Rv2140c ligand-binding site. Rv2140c is one of many conserved Mycobacterium tuberculosis proteins for which no molecular function has been identified. We have determined a high-resolution crystal structure of the Rv2140c gene product, which reveals a dimeric complex that shares strong structural homology with the phosphatidylethanolamine-binding family of proteins. Rv2140c forms low-millimolar interactions with a selection of soluble phosphatidylethanolamine analogs, indicating that it has a role in lipid metabolism. Furthermore, the small molecule locostatin binds to the Rv2140c ligand-binding site and also inhibits the growth of the model organism Mycobacterium smegmatis. Rv2140c and Rv2140cbind by molecular sieving (View interaction) Rv2140c and Rv2140cbind by cosedimentation in solution (View interaction) Rv2140c and Rv2140cbind by x-ray crystallography (View interaction)