3TH9

Crystal Structure of HIV-1 Protease Mutant Q7K V32I L63I with a cyclic sulfonamide inhibitor

Summary for 3TH9

• Entry DOI: 10.2210/pdb3th9/pdb
• Descriptor: Gag-Pol polyprotein, tert-butyl {(2S,3R)-4-[(4S)-7-fluoro-4-methyl-1,1-dioxido-4,5-dihydro-1,2-benzothiazepin-2(3H)-yl]-3-hydroxy-1-phenylbutan-2-yl}carbamate (3 entities in total)
• Functional Keywords: enzyme inhibition, aspartic protease, hiv/aids, conformational change, amprenavir, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus type 1 lw12.3 isolate (HIV-1)
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P0C6F2
• Total number of polymer chains: 2
• Total formula weight: 22594.82

Authors

Orth, P. (deposition date: 2011-08-18, release date: 2011-09-28, Last modification date: 2024-02-28)

Primary citation

Ganguly, A.K.,Alluri, S.S.,Caroccia, D.,Biswas, D.,Wang, C.H.,Kang, E.,Zhang, Y.,McPhail, A.T.,Carroll, S.S.,Burlein, C.,Munshi, V.,Orth, P.,Strickland, C.
Design, Synthesis, and X-ray Crystallographic Analysis of a Novel Class of HIV-1 Protease Inhibitors.
J.Med.Chem., 54:7176-7183, 2011

PubMed Abstract: In the present paper, design, synthesis, X-ray crystallographic analysis, and HIV-1 protease inhibitory activities of a novel class of compounds are disclosed. Compounds 28-30, 32, 35, and 40 were synthesized and found to be inhibitors of the HIV-1 protease. The crucial step in their synthesis involved an unusual endo radical cyclization process. Absolute stereochemistry of the three asymmetric centers in the above compounds have been established to be (4S,2'R,3'S) for optimal potency. X-ray crystallographic analysis has been used to determine the binding mode of the inhibitors to the HIV-1 protease.

PubMed: 21916489
DOI: 10.1021/jm200778q

Experimental method

X-RAY DIFFRACTION (1.34 Å)