title: 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.
authors.affiliation: EMBL c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Eulenburg
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Higman
authors.forename: Anne
authors.initials: A
authors.lastname: Diehl
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Holton
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D008024:Ligands; D050356:Lipid Metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology; D049488:Phosphatidylethanolamine Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D023303:Oxazolidinones; D049488:Phosphatidylethanolamine Binding Protein; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; C529490:locostatin
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