Structure of human cytidine deaminase bound to a potent inhibitor.
Human cytidine deaminase (CDA) is an enzyme prominent for its role in catalyzing metabolic processing of nucleoside-type anticancer and antiviral agents. It is thus a promising target for the development of small molecule therapeutic adjuvants. We report the first crystal structure of human CDA as a complex with a tight-binding inhibitor, diazepinone riboside 1. The structure reveals that inhibitor 1 is able to establish a canonical pi/pi-interaction with a key active site residue, Phe 137.
Chung
Sang J
SJ
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Fromme
J Christopher
JC
Verdine
Gregory L
GL
D001381:Azepines / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation
D001381:Azepines; D004791:Enzyme Inhibitors; C074608:diazepinone riboside; D003564:Cytidine Deaminase