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Publication Abstract from PubMed

Group A Streptococcus secretes cysteine proteases named Mac-1 and Mac-2 that mediate host immune evasion by targeting both IgG and Fc receptors. Here, we report the crystal structures of Mac-1 and its catalytically inactive C94A mutant in two different crystal forms. Despite the lack of sequence homology, Mac-1 adopts the canonical papain fold. Alanine mutations at the active site confirmed the critical residues involved in a papain-like catalytic mechanism. Mac-1 forms a symmetric dimer in both crystal forms and displays the unique dimer interface among papain superfamily members. Mutations at the dimer interface resulted in a significant reduction in IgG binding and catalysis, suggesting that the dimer contributes to both IgG specificity and enzyme cooperativity. A tunnel observed at the dimer interface constitutes a target for designing potential Mac-1-specific antimicrobial agents. The structures also offer insight into the functional difference between Mac-1 and Mac-2.

Crystal structure of group A streptococcus Mac-1: insight into dimer-mediated specificity for recognition of human IgG.,Agniswamy J, Nagiec MJ, Liu M, Schuck P, Musser JM, Sun PD Structure. 2006 Feb;14(2):225-35. PMID:16472742^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.