4OMC

X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba

Summary for 4OMC

• Entry DOI: 10.2210/pdb4omc/pdb
• Related: 1P8J 4OMD
• Related PRD ID: PRD_001220
• Descriptor: Furin, meta-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)benzamidine, FORMIC ACID, ... (6 entities in total)
• Functional Keywords: pro-protein convertase, serine protease, competitive inhibitor, protease-inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein: P09958
• Total number of polymer chains: 12
• Total formula weight: 320807.11

Authors

Dahms, S.O.,Than, M.E. (deposition date: 2014-01-27, release date: 2014-04-09, Last modification date: 2024-11-27)

Primary citation

Dahms, S.O.,Hardes, K.,Becker, G.L.,Steinmetzer, T.,Brandstetter, H.,Than, M.E.
X-ray Structures of Human Furin in Complex with Competitive Inhibitors.
Acs Chem.Biol., 9:1113-1118, 2014

PubMed Abstract: Furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including 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 noncovalent inhibitors. We show the inhibitor exchange by soaking, allowing the investigation of additional inhibitors and substrate analogues. Thus, our work provides a basis for the rational design of furin inhibitors.

PubMed: 24666235
DOI: 10.1021/cb500087x

Experimental method

X-RAY DIFFRACTION (2.3 Å)