2AVW

Crystal structure of monoclinic form of streptococcus Mac-1

Summary for 2AVW

• Entry DOI: 10.2210/pdb2avw/pdb
• Descriptor: IgG-degrading protease, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: mac-1, hydrolase
• Biological source: Streptococcus pyogenes
• Total number of polymer chains: 6
• Total formula weight: 211179.38

Authors

Agniswamy, J.,Nagiec, M.J.,Liu, M.,Schuck, P.,Musser, J.M.,Sun, P.D. (deposition date: 2005-08-30, release date: 2006-02-28, Last modification date: 2024-02-14)

Primary citation

Agniswamy, J.,Nagiec, M.J.,Liu, M.,Schuck, P.,Musser, J.M.,Sun, P.D.
Crystal structure of group a streptococcus mac-1: insight into dimer-mediated specificity for recognition of human IgG.
Structure, 14:225-235, 2006

PubMed Abstract: 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.

PubMed: 16472742
DOI: 10.1016/j.str.2005.10.012

Experimental method

X-RAY DIFFRACTION (2 Å)