3ou3 › Citations

Nine crystal structures determine the substrate envelope of the MDR HIV-1 protease.

Liu Z, Wang Y, Brunzelle J, Kovari IA, Kovari LC
Protein J 30 173-83 (2011)
Related entries: 3ots, 3oty, 3ou1, 3ou4, 3oua, 3oub, 3ouc, 3oud

Cited: 14 times
EuropePMC logo PMID: 21394574

Abstract

Under drug selection pressure, emerging mutations render HIV-1 protease drug resistant, leading to the therapy failure in anti-HIV treatment. It is known that nine substrate cleavage site peptides bind to wild type (WT) HIV-1 protease in a conserved pattern. However, how the multidrug-resistant (MDR) HIV-1 protease binds to the substrate cleavage site peptides is yet to be determined. MDR769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) was selected for present study to understand the binding to its natural substrates. MDR769 HIV-1 protease was co-crystallized with nine substrate cleavage site hepta-peptides. Crystallographic studies show that MDR769 HIV-1 protease has an expanded substrate envelope with wide open flaps. Furthermore, ligand binding energy calculations indicate weaker binding in MDR769 HIV-1 protease-substrate complexes. These results help in designing the next generation of HIV-1 protease inhibitors by targeting the MDR HIV-1 protease.

Reviews citing this publication (3)

  1. HIV Genome-Wide Protein Associations: a Review of 30 Years of Research. Li G, De Clercq E. Microbiol. Mol. Biol. Rev. 80 679-731 (2016)
  2. From base pair to bedside: molecular simulation and the translation of genomics to personalized medicine. Wright DW, Wan S, Shublaq N, Zasada SJ, Coveney PV. Wiley Interdiscip Rev Syst Biol Med 4 585-598 (2012)
  3. The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition. Fox JM, Zhao M, Fink MJ, Kang K, Whitesides GM. Annu Rev Biophys 47 223-250 (2018)

Articles citing this publication (11)

  1. HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Agniswamy J, Shen CH, Aniana A, Sayer JM, Louis JM, Weber IT. Biochemistry 51 2819-2828 (2012)
  2. Context surrounding processing sites is crucial in determining cleavage rate of a subset of processing sites in HIV-1 Gag and Gag-Pro-Pol polyprotein precursors by viral protease. Lee SK, Potempa M, Kolli M, Özen A, Schiffer CA, Swanstrom R. J. Biol. Chem. 287 13279-13290 (2012)
  3. The higher barrier of darunavir and tipranavir resistance for HIV-1 protease. Wang Y, Liu Z, Brunzelle JS, Kovari IA, Dewdney TG, Reiter SJ, Kovari LC. Biochem. Biophys. Res. Commun. 412 737-742 (2011)
  4. Correlating conformational shift induction with altered inhibitor potency in a multidrug resistant HIV-1 protease variant. de Vera IM, Blackburn ME, Fanucci GE. Biochemistry 51 7813-7815 (2012)
  5. Conserved hydrogen bonds and water molecules in MDR HIV-1 protease substrate complexes. Liu Z, Wang Y, Yedidi RS, Dewdney TG, Reiter SJ, Brunzelle JS, Kovari IA, Kovari LC. Biochem. Biophys. Res. Commun. 430 1022-1027 (2013)
  6. Insights into the mechanism of drug resistance: X-ray structure analysis of multi-drug resistant HIV-1 protease ritonavir complex. Liu Z, Yedidi RS, Wang Y, Dewdney TG, Reiter SJ, Brunzelle JS, Kovari IA, Kovari LC. Biochem. Biophys. Res. Commun. 431 232-238 (2013)
  7. Crystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance. Liu Z, Yedidi RS, Wang Y, Dewdney TG, Reiter SJ, Brunzelle JS, Kovari IA, Kovari LC. Biochem. Biophys. Res. Commun. 437 199-204 (2013)
  8. GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro. Amano M, Miguel Salcedo-Gómez P, Yedidi RS, Delino NS, Nakata H, Venkateswara Rao K, Ghosh AK, Mitsuya H. Sci Rep 7 12235 (2017)
  9. Ligand modifications to reduce the relative resistance of multi-drug resistant HIV-1 protease. Dewdney TG, Wang Y, Liu Z, Sharma SK, Reiter SJ, Brunzelle JS, Kovari IA, Woster PM, Kovari LC. Bioorg. Med. Chem. 21 7430-7434 (2013)
  10. A substrate selected by phage display exhibits enhanced side-chain hydrogen bonding to HIV-1 protease. Windsor IW, Raines RT. Acta Crystallogr D Struct Biol 74 690-694 (2018)
  11. The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. Chordia P, Dewdney TG, Keusch B, Kuiper BD, Ross K, Kovari IA, MacArthur R, Salimnia H, Kovari LC. Discoveries (Craiova) 2 e27 (2014)


Quick links