1C0T

CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH BM+21.1326

Summary for 1C0T

• Entry DOI: 10.2210/pdb1c0t/pdb
• Related: 1C0U 1klm 1rev 1rt1 1rt2 1rt3 1rt4 1rt5 1rt6 1rt7 1rth 1rti 1rtj 1rtv 1vru
• Descriptor: HIV-1 REVERSE TRANSCRIPTASE (A-CHAIN), HIV-1 REVERSE TRANSCRIPTASE (B-CHAIN), (R)-(+)9B-(3-METHYL)PHENYL-2,3-DIHYDROTHIAZOLO[2,3-A]ISOINDOL-5(9BH)-ONE, ... (4 entities in total)
• Functional Keywords: hiv-1 reverse transcriptase, aids, non-nucleoside inhibitor, drug design, transferase
• Biological source: Human immunodeficiency virus 1; More
• Cellular location: Matrix protein p17: Virion . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585 P04585
• Total number of polymer chains: 2
• Total formula weight: 116275.37

Authors

Ren, J.,Esnouf, R.M.,Hopkins, A.L.,Stuart, D.I.,Stammers, D.K. (deposition date: 1999-07-19, release date: 2000-07-19, Last modification date: 2024-10-30)

Primary citation

Ren, J.,Esnouf, R.M.,Hopkins, A.L.,Stuart, D.I.,Stammers, D.K.
Crystallographic analysis of the binding modes of thiazoloisoindolinone non-nucleoside inhibitors to HIV-1 reverse transcriptase and comparison with modeling studies.
J.Med.Chem., 42:3845-3851, 1999

PubMed Abstract: We have determined the crystal structures of thiazoloisoindolinone non-nucleoside inhibitors in complex with HIV-1 reverse transcriptase to high-resolution limits of 2.7 A (BM +21.1326) and 2. 52 A (BM +50.0934). We find that the binding modes of this series of inhibitors closely resemble that of "two-ring" non-nucleoside reverse transcriptase inhibitors. The structures allow rationalization of stereochemical requirements, structure-activity data, and drug resistance data. Comparisons with our previous structures suggest modifications to the inhibitors that might improve resilience to drug-resistant mutant forms of reverse transcriptase. Comparison with earlier modeling studies reveals that the predicted overlap of thiazoloisoindolinones with TIBO was largely correct, while that with nevirapine was significantly different.

PubMed: 10508433
DOI: 10.1021/jm990275t

Experimental method

X-RAY DIFFRACTION (2.7 Å)