Crystal structure of a major secreted protein of Mycobacterium tuberculosis—MPT63 at 1.5‐Å resolution

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Abstract
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‐Ångstrom resolution with the hope of yielding functional information about MPT63. The structure of MPT63 is an antiparallel β‐sandwich immunoglobulin‐like fold, with the unusual feature of the first β‐strand of the protein forming a parallel addition to the small antiparallel β‐sheet. MPT63 has weak structural similarity to many proteins with immunoglobulin folds, in particular, Homo sapiens β2‐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.