4TSX

HIV-1 Integrase Catalytic Core Domain Mutant Complexed with Allosteric Inhibitor

Summary for 4TSX

• Entry DOI: 10.2210/pdb4tsx/pdb
• Related: 1ITG
• Descriptor: Integrase, (2S)-tert-butoxy[4-(3,4-dihydro-2H-chromen-6-yl)-2-methylquinolin-3-yl]ethanoic acid, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hiv integrase, ccd, h171t, dde motif, dimer interface, allosteric inhibitor, allini, quinoline, dna binding protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 18713.01

Authors

Feng, L.,Kvaratskhelia, M. (deposition date: 2014-06-19, release date: 2014-12-17, Last modification date: 2024-11-13)

Primary citation

Slaughter, A.,Jurado, K.A.,Deng, N.,Feng, L.,Kessl, J.J.,Shkriabai, N.,Larue, R.C.,Fadel, H.J.,Patel, P.A.,Jena, N.,Fuchs, J.R.,Poeschla, E.,Levy, R.M.,Engelman, A.,Kvaratskhelia, M.
The mechanism of H171T resistance reveals the importance of N -protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase.
Retrovirology, 11:100-100, 2014

PubMed Abstract: Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are an important new class of anti-HIV-1 agents. ALLINIs bind at the IN catalytic core domain (CCD) dimer interface occupying the principal binding pocket of its cellular cofactor LEDGF/p75. Consequently, ALLINIs inhibit HIV-1 IN interaction with LEDGF/p75 as well as promote aberrant IN multimerization. Selection of viral strains emerging under the inhibitor pressure has revealed mutations at the IN dimer interface near the inhibitor binding site.

PubMed: 25421939
DOI: 10.1186/s12977-014-0100-1

Experimental method

X-RAY DIFFRACTION (1.94 Å)