title: The mycosins of Mycobacterium tuberculosis H37Rv: a family of subtilisin-like serine proteases.
abstract: There is little information regarding the role of proteolysis in Mycobacterium tuberculosis and no studies on the potential involvement of proteases in the pathogenesis of tuberculosis. We identified five M. tuberculosis genes (mycP1-5) that encode a family of serine proteases (mycosins-1 to 5), ranging from 36 to 47% identity. Each protein contains a catalytic triad (Asp, His, Ser) within highly conserved sequences, typical of proteases of the subtilisin family. These genes are also present in M. bovis BCG and other virulent mycobacteria, but only one homologue (mycP3) was detected in M. smegmatis. The mycosins have N-terminal signal sequences and C-terminal transmembrane anchors, and the localisation of the mycosins to the membrane/cell wall was verified by Western blot analysis of heterologously expressed proteins in cellular fractions of M. smegmatis. In M. tuberculosis, all the mycosins were expressed constitutively during growth in broth. Mycosins-2 and 3 were also expressed constitutively in M. bovis BCG, but no expression of mycosin-1 was detected. Mycosin-2 was modified by cleavage in all three mycobacterial species. The multiplicity and constitutive expression of these proteins suggests that they have an important role in the biology of M. tuberculosis.
authors.affiliation: Department of Medical Biochemistry/MRC Centre for Molecular and Cellular Biology, University of Stellenbosch, 7505, Tygerberg, South Africa. gbrown@molbiol.ox.ac.uk
authors.forename: G D
authors.initials: GD
authors.lastname: Brown
authors.forename: J A
authors.initials: JA
authors.lastname: Dave
authors.forename: N C
authors.initials: NC
authors.lastname: Gey van Pittius
authors.forename: L
authors.initials: L
authors.lastname: Stevens
authors.forename: M R
authors.initials: MR
authors.lastname: Ehlers
authors.forename: A D
authors.initials: AD
authors.lastname: Beyers
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D016208:Databases, Factual; D015971:Gene Expression Regulation, Enzymologic; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000235:genetics; D020102:Mycobacterium smegmatis / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D010802:Phylogeny; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D020860:Subtilisin / Q000235:genetics / Q000378:metabolism
chemical_list: D012697:Serine Endopeptidases; D020860:Subtilisin