title: The structure of Mycobacterium tuberculosis MPT51 (FbpC1) defines a new family of non-catalytic alpha/beta hydrolases.
abstract: Mycobacterium tuberculosis, the causative agent of tuberculosis, is known to secrete a number of highly immunogenic proteins that are thought to confer pathogenicity, in part, by mediating binding to host tissues. Among these secreted proteins are the trimeric antigen 85 (Ag85) complex and the related MPT51 protein, also known as FbpC1. While the physiological function of Ag85, a mycolyltransferase required for the biosynthesis of the cell wall component alpha,alpha'-trehalose dimycolate (or cord factor), has been identified recently, the function of the closely related MPT51 (approximately 40% identity with the Ag85 components) remains to be established. The crystal structure of M.tuberculosis MPT51, determined to 1.7 A resolution, shows that MPT51, like the Ag85 components Ag85B and Ag85C2, folds as an alpha/beta hydrolase, but it does not contain any of the catalytic elements required for mycolyltransferase activity. Moreover, the absence of a recognizable alpha,alpha'-trehalose monomycolate-binding site and the failure to detect an active site suggest that the function of MPT51 is of a non-enzymatic nature and that MPT51 may in fact represent a new family of non-catalytic alpha/beta hydrolases. Previous experimental evidence and the structural similarity to some integrins and carbohydrate-binding proteins led to the hypothesis that MPT51 might have a role in host tissue attachment, whereby ligands may include the serum protein fibronectin and small sugars.
authors.affiliation: School of Biosciences, The University of Birmingham, Edgabston, Birmingham B15 2TT, UK.
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Wilson
authors.forename: William N
authors.initials: WN
authors.lastname: Maughan
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Klaus
authors.initials: K
authors.lastname: Fütterer
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D003311:Cord Factors / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D005353:Fibronectins / Q000378:metabolism; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003311:Cord Factors; D005353:Fibronectins; C082911:MPT51 protein, Mycobacterium; D011994:Recombinant Proteins; C461642:antigen 85C2, Mycobacterium tuberculosis; C021099:trehalose monomycolate; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis; C053820:trehalose mycolyltransferase