Histidine and aspartic acid residues important for immunoglobulin G endopeptidase activity of the group A Streptococcus opsonophagocytosis-inhibiting Mac protein

Benfang Lei, Mengyao Liu, Elishia G. Meyers, Heather M. Manning, Michael J. Nagiec, James M. Musser

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The secreted Mac protein made by serotype M1 group A Streptococcus (GAS) (designated Mac5005) inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear neutrophils. This protein also has cysteine endopeptidase activity against human immunoglobulin G (IgG). Site-directed mutagenesis was used to identify histidine and aspartic acid residues important for Mac IgG endopeptidase activity. Replacement of His262 with Ala abolished Mac5005 IgG endopeptidase activity. Asp284Ala and Asp286Ala mutant proteins had compromised enzymatic activity, whereas 21 other Asp-to-Ala mutant proteins cleaved human IgG at the apparent wild-type level. The results suggest that His262 is an active-site residue and that Asp284 and Asp286 are important for the enzymatic activity or structure of Mac protein. These Mac mutants provide new information about structure-activity relationships in this protein and will assist study of the mechanism of inhibition of opsonophagocytosis and killing of GAS by Mac.

Original languageEnglish (US)
Pages (from-to)2881-2884
Number of pages4
JournalInfection and Immunity
Volume71
Issue number5
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Histidine and aspartic acid residues important for immunoglobulin G endopeptidase activity of the group A Streptococcus opsonophagocytosis-inhibiting Mac protein'. Together they form a unique fingerprint.

Cite this