5fce

Publication Abstract from PubMed

Antimicrobial resistant and hospital-adapted Enterococcus faecium represents a clinical problem in immunocompromized patients in hospitals worldwide. Understanding the molecular pathogenesis of E. faecium infections may provide for novel therapies to treat or prevent infections. A potential target for novel treatment therapies is the serine-glutamate repeat containing protein A (SgrA), which is a cell wall-anchored LPxTG surface protein implicated in binding to fibrinogen and nidogen. Here we report the x-ray crystal structure of the N-terminal ligand binding domain of SgrA (rSgrA28-153 ) to a resolution of 1.79 A. The structure revealed a new protein fold with significant differences from previously characterized DEv-IgG- and inv-IgG-like folds of adhesive proteins known as microbial surface components recognizing adhesive matrix molecules. The structure contains a Lys-Asn-Glu triad with the potential to form a Lys-Asn isopeptide bond. However, even in the absence of a stabilizing intramolecular isopeptide bond, rSgrA28-153 exhibits remarkable properties like resistance to proteases and high thermal stability. The interaction of rSgrA28-153 with fibrinogen, nidogen, laminin and abiotic surfaces has been characterized and rSgrA28-153 binds to these molecules with high affinity. rSgrA28-153 also binds to the beta chain of fibrinogen and with high affinity and specificity. Strikingly, the presence of 29 surface-exposed hydrophobic amino acid residues likely play an important role in the selectivity of rSgrA28-153 to bind to different abiotic surfaces. The results obtained from this study have opened new avenues to explore and understand the role of this unique surface adhesin in the pathogenesis of catheter-related infections. This article is protected by copyright. All rights reserved.

The crystal structure of the ligand binding region of Serine-glutamate repeat protein A (SgrA) of Enterococcus faecium reveals a new protein fold: functional characterization and insights into its adhesion function.,Nagarajan R, Hendrickx AP, Ponnuraj K FEBS J. 2016 Jun 23. doi: 10.1111/febs.13792. PMID:27334767^[1]

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