6HZA

X-ray structure of furin in complex with the cyclic peptide c[glutaryl-Arg-Arg-Lys]-Arg-4-Amba

6HZA の概要

• エントリーDOI: 10.2210/pdb6hza/pdb
• 分子名称: Furin, ARG-ARG-LYS-ARG-00S, CALCIUM ION, ... (9 entities in total)
• 機能のキーワード: protease proprotein convertase inhibitor complex cyclic peptide, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53731.40

構造登録者

Dahms, S.O. (登録日: 2018-10-23, 公開日: 2019-02-06, 最終更新日: 2024-11-13)

主引用文献

Van Lam van, T.,Ivanova, T.,Hardes, K.,Heindl, M.R.,Morty, R.E.,Bottcher-Friebertshauser, E.,Lindberg, I.,Than, M.E.,Dahms, S.O.,Steinmetzer, T.
Design, Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin.
Chemmedchem, 14:673-685, 2019

PubMed Abstract: The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.

PubMed: 30680958
DOI: 10.1002/cmdc.201800807

実験手法

X-RAY DIFFRACTION (1.9 Å)