Format

Send to

Choose Destination
See comment in PubMed Commons below
Pharmacol Rev. 2008 Mar;60(1):128-41. doi: 10.1124/pr.107.07110. Epub 2008 Mar 5.

Sortase as a target of anti-infective therapy.

Author information

1
Department of Microbiology, University of Chicago, Chicago, IL 60637, USA.

Abstract

The rise in antibiotic-resistant bacteria is a major concern, in particular because it includes many different species of pathogenic microbes. These "superbugs" are further characterized by high levels of virulence and disease-associated mortality. There seems to be few new antibiotics in the drug discovery pipeline; recent work has sought to define and validate new drug targets. The assembly of surface proteins and pili in the cell wall envelope of Gram-positive bacteria is catalyzed by sortase. Sortase cleaves a conserved C-terminal sequence of these polypeptides to generate an acyl-enzyme intermediate. The acyl-enzyme is next resolved by nucleophilic attack by the amino groups within cell wall cross-bridges or pilin proteins, thereby covalently attaching the polypeptides to the cell wall or the next pilin subunit. Sortase substrates function as adhesins, internalins, blood clotting and immune evasion factors, and transporters for nutrients across the microbial cell wall envelope; without them, most pathogens cannot sustain an infection. Here we review what is known about sortase catalysis and surface protein function, how surface protein anchoring can be inhibited, and what prospects such inhibition may have for anti-infective therapy.

PMID:
18321961
DOI:
10.1124/pr.107.07110
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center