The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant

Bujacz, G.; Alexandratos, Jerry; Zhou-Liu, Qing; Clement-Mella, C.; Wlodawer, Alexander

doi:10.1016/s0014-5793(96)01236-7

Cited by 107 publications

(99 citation statements)

References 15 publications

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“…Residues 138-149 in the active site region, and residues 186-194 between the ␣5 and ␣6 helices, are flexible loops in poorly defined density, as previously noted in other unliganded core domain structures (12,26,31). However, residues 138-141 and 145-149 could be interpreted in monomer A, and the 186-194 loop in both monomers could be built into weak density based on its location in the 1.6-Å resolution IN 52-210 structure.…”

Section: Resultsmentioning

confidence: 55%

See 1 more Smart Citation

Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: A model for viral DNA binding

Chen

Krucinski

Miercke

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

384

440

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Section: Resultsmentioning

confidence: 55%

“…The introduction of five mutations, C56S, W131D, F139D, F185K, and C280S, did not alter the structure of the catalytic core compared with other structures containing only one of these four mutations, F185K (12), or mutation F185H (26,31). The finding of an identical catalytic core domain structure (44) and RASTER3D (45).…”

Section: Discussionmentioning

confidence: 84%

Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: A model for viral DNA binding

Chen

Krucinski

Miercke

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

384

440

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“…The N-terminal domain (NTD, residues 1-46) contains the zinc-binding HHCC motif, which is essential for the correct folding of this domain and function of the full-length protein (17)(18)(19)(20)(21)(22). The catalytic core domain (CCD, residues 56 -202) contains the DDE active site, which coordinates catalytic Mg 2ϩ ions and mediates catalysis of both 3Ј-processing and strand transfer reactions (23)(24)(25)(26)(27). The C-terminal domain (CTD, residues 220 -288) has a SH3-like fold (28 -30).…”

Section: Hiv-1 Integrase (In)mentioning

confidence: 99%

A Critical Role of the C-terminal Segment for Allosteric Inhibitor-induced Aberrant Multimerization of HIV-1 Integrase

Shkriabai

Dharmarajan

Slaughter

et al. 2014

Journal of Biological Chemistry

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Background: Allosteric integrase (IN) inhibitors (ALLINIs) promote aberrant protein multimerization. Results: ALLINI-2 induces protein-protein interactions, including C-terminal residues Lys-264 and Lys-266, which lead to aberrant, higher-order IN multimerization. Conclusion: The protein-protein contacts beyond the inhibitor binding site contribute to aberrant IN multimerization. Significance: Our findings provide structural clues and underscore the significance for exploiting IN multimerization as a new therapeutic target.

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“…Among these structures, only 1BL3 [28] and 2ITG [29] contain the flexible loop that consists of residues between 140-149. After identifying a crystal structure of catalytic core domain with a ligand (5CITEP: 1-(5-chloro-1H-indol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)) [30], IN catches attention as a new target of antiviral drug studies.…”

Section: Human Immunodeficiency Virus (Hiv) Is a Member Of Lentivirusmentioning

confidence: 99%

Docking and Molecular Dynamics Calculations of Some Previously Studied and newly Designed Ligands to Catalytic Core Domain of HIV-1 Integrase and an Investigation to Effects of Conformational Changes of Protein on Docking Results

Ercan¹

2016

Journal of the Turkish Chemical Society, Section A: Chemistry

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Nowadays, AIDS still remains as a worldwide pandemic and continues to cause many deaths which arise from HIV-1 virus. For nearly 35 years, drugs that target various steps of virus life cycle have been developed. HIV-1 integrase constitutes one of these steps which is essential for virus life cycle. Computer-aided drug design is being used in many drug development and drug improvement studies as also used in development of the first HIV-1 integrase inhibitor Raltegravir. In this study, 3 ligands which are already used as HIV-1 integrase inhibitors and 4 newly designed ligands were docked to catalytic core domain of HIV-1 integrase. Each ligand docked to three different conformations of protein. Prepared complexes (21 items) were carried out by 50 ns MD simulations and results were analyzed. Finally, the binding free energies of ligands were calculated. It was determined that designed ligands L01 and L03 gave favorable results. The questions about the ligands which have low docking scores in a conformation of protein could give better scores in another conformation of protein and if the MD simulations carry the different oriented and different localized ligands in same position at the end of simulation were answered.

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The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant

Cited by 107 publications

References 15 publications

Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: A model for viral DNA binding

Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: A model for viral DNA binding

A Critical Role of the C-terminal Segment for Allosteric Inhibitor-induced Aberrant Multimerization of HIV-1 Integrase

Docking and Molecular Dynamics Calculations of Some Previously Studied and newly Designed Ligands to Catalytic Core Domain of HIV-1 Integrase and an Investigation to Effects of Conformational Changes of Protein on Docking Results

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