Reduced HIV-1 integrase flexibility as a mechanism for raltegravir resistance

Journal of Structural Biology

Volumn 184, Issue 2, 2013, Pages 245-250

  Dewdney, Tamaria G ^a   Wang, Yong ^a   Kovari, Iulia A ^a   Reiter, Samuel J ^a   Kovari, Ladislau C ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Drug resistance; HIV 1 integrase; Molecular dynamics; NAMD; Raltegravir

Indexed keywords

INTEGRASE; RALTEGRAVIR;

ANTIVIRAL RESISTANCE; ARTICLE; BINDING SITE; CATALYSIS; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DRUG PROTEIN BINDING; ENZYME ACTIVE SITE; ENZYME MECHANISM; GENE MUTATION; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN SECONDARY STRUCTURE; PROTEIN STRUCTURE; SIMULATION; STRUCTURE ANALYSIS; VIRUS GENOME; VIRUS MUTANT; VIRUS RESISTANCE; WILD TYPE;

HUMAN IMMUNODEFICIENCY VIRUS 1;

DRUG RESISTANCE; HIV-1 INTEGRASE; MOLECULAR DYNAMICS; NAMD; RALTEGRAVIR;

AMINO ACID SUBSTITUTION; CATALYTIC DOMAIN; DRUG RESISTANCE, VIRAL; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; MOLECULAR DYNAMICS SIMULATION; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; PYRROLIDINONES; THERMODYNAMICS;

EID: 84887238860     PISSN: 10478477     EISSN: 10958657     Source Type: Journal    
DOI: 10.1016/j.jsb.2013.07.008     Document Type: Article

References (32)

1. Arnold K., et al. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 2006, 22(2):195-201.
2. Balaraju T., et al. Aromatic interaction profile to understand the molecular basis of raltegravir resistance. Struct. Chem. 2012, 1-14.
3. Berman H.M., et al. The Protein Data Bank. Nucleic Acids Res. 2000, 28(1):235-242.
4. Cooper D.A., et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N. Engl. J. Med. 2008, 359(4):355-365.
5. DeLano, W., 2007. The PyMol Molecular Graphics System, Version 1.3, Shrödinger, LLC.
6. Engelman A., Craigie R. Efficient magnesium-dependent human immunodeficiency virus type 1 integrase activity. J. Virol. 1995, 69(9):5908-5911.
7. Espeseth A.S., et al. HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase. Proc. Natl. Acad. Sci. USA 2000, 97(21):11244-11249.
8. Grobler J.A., et al. Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes. Proc. Natl. Acad. Sci. USA 2002, 99(10):6661-6666.
9. Hare S., et al. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 2010, 464(7286):232-236.
10. Hightower K.E., et al. Dolutegravir (S/GSK1349572) exhibits significantly slower dissociation than raltegravir and elvitegravir from wild-type and integrase inhibitor-resistant HIV-1 integrase-DNA complexes. Antimicrob. Agents Chemother. 2011, 55(10):4552-4559.
11. Hsu C.K., Park S. Computational and mutagenesis studies of the streptavidin native dimer interface. J. Mol. Graph Model 2010, 29(3):295-308.
12. Hu Z., Kuritzkes D.R. Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. J. Acquir. Immune. Defic. Syndr. 2010, 55(2):148-155.
13. Hu J.P., et al. Study on the interactions between diketo-acid inhibitors and prototype foamy virus integrase-DNA complex via molecular docking and comparative molecular dynamics simulation methods. J. Biomol. Struct. Dyn. 2013, 31(7):734-747.
14. Huang M., Grant G.H., Richards W.G. Binding modes of diketo-acid inhibitors of HIV-1 integrase: a comparative molecular dynamics simulation study. J. Mol. Graph Model 2011, 29(7):956-964.
15. Humphrey W., Dalke A., Schulten K. VMD: visual molecular dynamics. J. Mol. Graph 1996, 14(1):33-38. 27-8.
16. Kawasuji T., et al. A platform for designing HIV integrase inhibitors. Part 1: 2-hydroxy-3-heteroaryl acrylic acid derivatives as novel HIV integrase inhibitor and modeling of hydrophilic and hydrophobic pharmacophores. Bioorg. Med. Chem. 2006, 14(24):8430-8445.
17. Kawasuji T., et al. A platform for designing HIV integrase inhibitors. Part 2: a two-metal binding model as a potential mechanism of HIV integrase inhibitors. Bioorg. Med. Chem. 2006, 14(24):8420-8429.
18. Krishnan L., et al. Structure-based modeling of the functional HIV-1 intasome and its inhibition. Proc. Natl. Acad. Sci. USA 2010, 107(36):15910-15915.
19. Lee M.C., et al. Large-scale conformational dynamics of the HIV-1 integrase core domain and its catalytic loop mutants. Biophys. J. 2005, 88(5):3133-3146.
20. MacKerell A.D., et al. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 1998, 102(18):3586-3616.
21. Maignan S., et al. Crystal structures of the catalytic domain of HIV-1 integrase free and complexed with its metal cofactor: high level of similarity of the active site with other viral integrases. J. Mol. Biol. 1998, 282(2):359-368.
22. Perryman A.L., et al. A dynamic model of HIV integrase inhibition and drug resistance. J. Mol. Biol. 2010, 397(2):600-615.
23. Phillips J.C., et al. Scalable molecular dynamics with NAMD. J. Comput. Chem. 2005, 26(16):1781-1802.
24. Pommier Y., Johnson A.A., Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat. Rev. Drug. Discov. 2005, 4(3):236-248.
25. Pommier Y., et al. Biochemical and Pharmacological Analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir. Biochemistry 2010, 49(17):3715-3722.
26. Rose R.B., Craik C.S., Stroud R.M. Domain flexibility in retroviral proteases: structural implications for drug resistant mutations. Biochemistry 1998, 37(8):2607-2621.
27. Serrao E., et al. Raltegravir, elvitegravir and metoogravir: the birth of "me-too" HIV-1 integrase inhibitors. Retrovirology 2009, 6:25.
28. Sotomayor M., Schulten K. Molecular dynamics study of gating in the mechanosensitive channel of small conductance MscS. Biophys. J. 2004, 87(5):3050-3065.
29. Summa V., et al. Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J. Med. Chem. 2008, 51(18):5843-5855.
30. Xie X.-Q. Molecular modeling and in silico drug design. Foye's Principles of Medicinal Chemistry 2008, 54-66. Lippincott Williams & Wilkins, Philadelphia. T.L. Lemke (Ed.).
31. Xue W., et al. Understanding the structural and energetic basis of inhibitor and substrate bound to the full-length NS3/4A: insights from molecular dynamics simulation, binding free energy calculation and network analysis. Mol. Biosyst. 2012, 8(10):2753-2765.
32. Xue W., et al. Exploring the molecular mechanism of cross-resistance to HIV-1 integrase strand transfer inhibitors by molecular dynamics simulation and residue interaction network analysis. J. Chem. Inf. Model. 2013, 53(1):210-222.