Rapid X-ray diffraction analysis of HIV-1 protease-inhibitor complexes: inhibitor exchange in single crystals of the bound enzyme.
The ability to replace an inhibitor bound to the HIV-1 protease in single crystals with other potent inhibitors offers the possibility of investigating a series of protease inhibitors rapidly and conveniently with the use of X-ray crystallography. This approach affords a fast turnaround of structural information for iterative rational drug designs and obviates the need for studying the complex structures by co-crystallization. The replacement approach has been successfully used with single crystals of the HIV-1 protease complexed with a weak inhibitor. The structures of the complexes obtained by the replacement method are similar to those determined by co-crystallization.
Munshi
S
S
Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA.
Chen
Z
Z
Li
Y
Y
Olsen
D B
DB
Fraley
M E
ME
Hungate
R W
RW
Kuo
L C
LC
D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation
D017320:HIV Protease Inhibitors; D046911:Macromolecular Substances; D016333:HIV Protease