Open AccessHigh‐resolution crystal structures of factor XIa coagulation factor in complex with nonbasic high‐affinity synthetic inhibitors
Author(s) -
Fradera Xavier,
Kazemier Bert,
Carswell Emma,
Cooke Andrew,
Oubrie Arthur,
Hamilton William,
Dempster Maureen,
Krapp Stephan,
Nagel Susanna,
Jestel Anja
Publication year - 2012
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309112009037
Subject(s) - coagulation , active site , resolution (logic) , stereochemistry , chemistry , enzyme , biochemistry , computer science , artificial intelligence , psychology , psychiatry
Factor XI (FXI) is a key enzyme in the coagulation pathway and an attractive target for the development of anticoagulant drugs. A small number of high‐resolution crystal structures of FXIa in complex with small synthetic inhibitors have been published to date. All of these ligands have a basic P1 group and bind exclusively in the nonprime side of the active site of FXIa. Here, two structures of FXIa in complex with nonbasic inhibitors that occupy both the prime and nonprime sides of the active site are presented. These new structures could be valuable in the design and optimization of new FXIa synthethic inhibitors.