tetano
Editor, Senior Moderator
ACS Chem Biol. 2014 Mar 25. [Epub ahead of print]
X-ray structures of human furin in complex with competitive inhibitors.
Dahms SO, Hardes K, Becker GL, Steinmetzer T, Brandstetter H, Than ME.
Abstract
Furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including e.g. the highly lethal bacillus anthracis or the pandemic influenza virus. Development and improvement of inhibitors for pharmacological use require a detailed knowledge of the protease's substrate and inhibitor binding properties. Here we present a novel preparation of human furin and the first crystal structures of this enzyme in complex with non-covalent inhibitors. We show the inhibitor-exchange by soaking, allowing the investigation of additional inhibitors and substrate analogues. Thus, our work provides the basis for rational design of furin inhibitors.
PMID:
24666235
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24666235
X-ray structures of human furin in complex with competitive inhibitors.
Dahms SO, Hardes K, Becker GL, Steinmetzer T, Brandstetter H, Than ME.
Abstract
Furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including e.g. the highly lethal bacillus anthracis or the pandemic influenza virus. Development and improvement of inhibitors for pharmacological use require a detailed knowledge of the protease's substrate and inhibitor binding properties. Here we present a novel preparation of human furin and the first crystal structures of this enzyme in complex with non-covalent inhibitors. We show the inhibitor-exchange by soaking, allowing the investigation of additional inhibitors and substrate analogues. Thus, our work provides the basis for rational design of furin inhibitors.
PMID:
24666235
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24666235