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

Abstract

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.

Keywords: CR; DHPE; DHPG; DHPS; ITC; PE; PEBP; Structural biology; Tuberculosis; conserved region; dihexanoyl phosphatidylethanolamine; dihexanoyl phosphatidylglycerol; dihexanoyl phosphatidylserine; isothermal titration calorimetry; phosphatidylethanolamine; phosphatidylethanolamine-binding protein.