Crystal structure of a major secreted protein of Mycobacterium tuberculosis-MPT63 at 1.5-A resolution.
MPT63 is a small, major secreted protein of unknown function from Mycobacterium tuberculosis that has been shown to have immunogenic properties and has been implicated in virulence. A BLAST search identified that MPT63 has homologs only in other mycobacteria, and is therefore mycobacteria specific. As MPT63 is a secreted protein, mycobacteria specific, and implicated in virulence, MPT63 is an attractive drug target against the deadliest infectious disease, tuberculosis (TB). As part of the TB Structural Genomics Consortium, the X-ray crystal structure of MPT63 was determined to 1.5-Angstrom resolution with the hope of yielding functional information about MPT63. The structure of MPT63 is an antiparallel beta-sandwich immunoglobulin-like fold, with the unusual feature of the first beta-strand of the protein forming a parallel addition to the small antiparallel beta-sheet. MPT63 has weak structural similarity to many proteins with immunoglobulin folds, in particular, Homo sapiens beta2-adaptin, bovine arrestin, and Yersinia pseudotuberculosis invasin. Although the structure of MPT63 gives no conclusive evidence to its function, structural similarity suggests that MPT63 could be involved in cell-host interactions to facilitate endocytosis/phagocytosis.
Goulding
Celia W
CW
Howard Hughes Medical Institute, University of California at Los Angeles-DOE, Center for Genomics and Proteomics, Los Angeles 90095, USA.
Parseghian
Angineh
A
Sawaya
Michael R
MR
Cascio
Duilio
D
Apostol
Marcin I
MI
Gennaro
Maria Laura
ML
Eisenberg
David
D
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017385:Sequence Homology; D055672:Static Electricity
D001426:Bacterial Proteins; C103339:MPT63 antigen, Mycobacterium tuberculosis