Crystal structure of the HIV-1 integrase core domain in complex with sucrose reveals details of an allosteric inhibitory binding site.
HIV integrase (IN) is an essential enzyme in HIV replication and an important target for drug design. IN has been shown to interact with a number of cellular and viral proteins during the integration process. Disruption of these important interactions could provide a mechanism for allosteric inhibition of IN. We present the highest resolution crystal structure of the IN core domain to date. We also present a crystal structure of the IN core domain in complex with sucrose which is bound at the dimer interface in a region that has previously been reported to bind integrase inhibitors.
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia.
Jerome
J
Wielens
Stephen J
SJ
Headey
Dharshini
D
Jeevarajah
David I
DI
Rhodes
John
J
Deadman
David K
DK
Chalmers
Martin J
MJ
Scanlon
Michael W
MW
Parker
D000494:Allosteric Regulation; D001665:Binding Sites; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D005990:Glycerol / Q000378:metabolism; D019427:HIV Integrase / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013395:Sucrose / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D019428:HIV Integrase Inhibitors; D013395:Sucrose; D019427:HIV Integrase; D005990:Glycerol