4O44

Crystal Structure of HIV-1 Reverse Transcriptase in complex with 4-((4-(mesitylamino)-6-(3-morpholinopropoxy)-1,3,5-triazin-2-yl)amino)benzonitrile (JLJ529), a non-nucleoside inhibitor

Summary for 4O44

• Entry DOI: 10.2210/pdb4o44/pdb
• Related: 1S9E 2ZD1 4KKO 4O4G
• Descriptor: HIV-1 reverse transcriptase, p66 subunit, HIV-1 reverse transcriptase, p51 subunit, 4-({4-[3-(morpholin-4-yl)propoxy]-6-[(2,4,6-trimethylphenyl)amino]-1,3,5-triazin-2-yl}amino)benzonitrile, ... (4 entities in total)
• Functional Keywords: polymerase, rnase, reverse transcription, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus type 1 BH10 (HIV-1); More
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03366 P03366
• Total number of polymer chains: 2
• Total formula weight: 114502.30

Authors

Mislak, A.C.,Frey, K.M.,Anderson, K.S. (deposition date: 2013-12-18, release date: 2014-05-21, Last modification date: 2023-09-20)

Primary citation

Mislak, A.C.,Frey, K.M.,Bollini, M.,Jorgensen, W.L.,Anderson, K.S.
A mechanistic and structural investigation of modified derivatives of the diaryltriazine class of NNRTIs targeting HIV-1 reverse transcriptase.
Biochim.Biophys.Acta, 1840:2203-2211, 2014

PubMed Abstract: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are vital in treating HIV-1 infection by inhibiting reverse transcriptase (RT). Drug toxicity and resistance drive the need for effective new inhibitors with improved physiochemical properties and potent antiviral activity. Computer-aided and structure-based drug design have guided the addition of solubilizing substituents to the diaryltriazine scaffold. These derivatives have markedly improved solubility and maintain low nanomolar antiviral activity against RT. The molecular and structural basis of inhibition for this series was determined to facilitate future inhibitor development with improved pharmacological profiles.

PubMed: 24726448
DOI: 10.1016/j.bbagen.2014.04.001

Experimental method

X-RAY DIFFRACTION (2.889 Å)