Structural and Thermodynamic Basis of Amprenavir/Darunavir and Atazanavir Resistance in HIV-1 Protease with Mutations at Residue 50

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Published in:	Journal of Virology Vol. 87; no. 8; pp. 4176 - 4184
Main Authors:	Seema Mittal, Rajinthna M. Bandaranayake, Nancy M. King, Moses Prabu-Jeyabalan, Madhavi N. L. Nalam, Ellen A. Nalivaika, Nese Kurt Yilmaz, Celia A. Schiffer
Format:	Journal Article
Language:	English
Published:	United States American Society for Microbiology 01-04-2013
Subjects:	Anti-HIV Agents - pharmacology Atazanavir Sulfate Carbamates - pharmacology Crystallography, X-Ray Darunavir Drug Resistance, Viral HIV Protease - chemistry HIV Protease - genetics HIV-1 - drug effects HIV-1 - genetics Humans Kinetics Models, Molecular Mutant Proteins - chemistry Mutant Proteins - genetics Mutation, Missense Oligopeptides - pharmacology Point Mutation Protein Binding Protein Conformation Pyridines - pharmacology Sulfonamides - pharmacology Thermodynamics Vaccines and Antiviral Agents
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Abstract	Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI
AbstractList	Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the protease flap tips, closing the active site upon ligand binding. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. To explain how APV, DRV, and ATV susceptibility are influenced by mutations at residue 50 in HIV-1 protease, structural and binding thermodynamics studies were carried out on I50V/L-substituted protease variants in the compensatory mutation A71V background. Reduced affinity to both I50V/A71V and I50L/A71V double mutants is largely due to decreased binding entropy, which is compensated for by enhanced enthalpy for ATV binding to I50V variants and APV binding to I50L variants, leading to hypersusceptibility in these two cases. Analysis of the crystal structures showed that the substitutions at residue 50 affect how APV, DRV, and ATV bind the protease with altered van der Waals interactions and that the selection of I50V versus I50L is greatly influenced by the chemical moieties at the P1 position for APV/DRV and the P2 position for ATV. Thus, the varied inhibitor susceptibilities of I50V/L protease variants are largely a direct consequence of the interdependent changes in protease inhibitor interactions. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI
Author	Rajinthna M. Bandaranayake Ellen A. Nalivaika Nese Kurt Yilmaz Seema Mittal Celia A. Schiffer Madhavi N. L. Nalam Nancy M. King Moses Prabu-Jeyabalan
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Notes	S.M., R.M.B., and N.M.K. contributed equally to this article. Present address: Rajinthna M. Bandaranayake, Skirball Institute, New York University Medical School, New York, New York, USA; Moses Prabu-Jeyabalan, Department of Molecular Biology, The Commonwealth Medical, College, Scranton, Pennsylvania, USA.
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References	e_1_3_2_26_2 e_1_3_2_27_2 e_1_3_2_28_2 e_1_3_2_29_2 e_1_3_2_41_2 e_1_3_2_40_2 e_1_3_2_20_2 e_1_3_2_43_2 e_1_3_2_21_2 e_1_3_2_42_2 e_1_3_2_22_2 Tisdale M (e_1_3_2_13_2) 1999 e_1_3_2_23_2 e_1_3_2_24_2 e_1_3_2_25_2 Colonno R (e_1_3_2_16_2) 2004 Van Marck H (e_1_3_2_14_2) 2007; 12 Elston R (e_1_3_2_37_2) 2006; 11 e_1_3_2_9_2 e_1_3_2_15_2 DeLano WL (e_1_3_2_30_2) 2002 e_1_3_2_38_2 e_1_3_2_8_2 e_1_3_2_17_2 e_1_3_2_6_2 e_1_3_2_18_2 e_1_3_2_39_2 e_1_3_2_19_2 e_1_3_2_32_2 e_1_3_2_10_2 e_1_3_2_31_2 e_1_3_2_11_2 e_1_3_2_34_2 e_1_3_2_4_2 e_1_3_2_12_2 e_1_3_2_33_2 e_1_3_2_3_2 e_1_3_2_36_2 e_1_3_2_2_2 e_1_3_2_35_2 Roberts NA (e_1_3_2_5_2) 1995; 9 Henderson LE (e_1_3_2_7_2) 1988
References_xml	– ident: e_1_3_2_19_2 doi: 10.1097/00002030-199912030-00006 – ident: e_1_3_2_32_2 doi: 10.1128/AAC.00574-10 – ident: e_1_3_2_18_2 doi: 10.1093/nar/gkg100 – volume: 11 start-page: S102 year: 2006 ident: e_1_3_2_37_2 article-title: De-selection for the I50V mutation occurs in clinical isolates during Aptivus/r (tipranavir/ritonavir) based therapy publication-title: Antivir. Ther. contributor: fullname: Elston R – ident: e_1_3_2_28_2 doi: 10.1007/978-1-4612-3374-9_13 – volume-title: Abstr. Conf. Retroviruses Opportunistic Infect. year: 2004 ident: e_1_3_2_16_2 contributor: fullname: Colonno R – ident: e_1_3_2_25_2 doi: 10.1107/S0907444994003112 – ident: e_1_3_2_35_2 doi: 10.1021/jm049560p – ident: e_1_3_2_31_2 doi: 10.1128/JVI.02531-09 – ident: e_1_3_2_26_2 doi: 10.1128/JVI.80.7.3607-3616.2006 – ident: e_1_3_2_8_2 doi: 10.1007/978-1-4615-5373-1_2 – ident: e_1_3_2_9_2 doi: 10.1345/aph.10423 – ident: e_1_3_2_33_2 doi: 10.1128/JVI.02706-06 – volume: 9 start-page: S27 year: 1995 ident: e_1_3_2_5_2 article-title: Drug-resistance patterns of saquinavir and other HIV proteinase inhibitors publication-title: AIDS contributor: fullname: Roberts NA – ident: e_1_3_2_2_2 doi: 10.1089/aid.1992.8.153 – ident: e_1_3_2_12_2 doi: 10.1128/jvi.69.9.5228-5235.1995 – ident: e_1_3_2_38_2 doi: 10.2217/17469600.1.3.291 – ident: e_1_3_2_39_2 doi: 10.1111/j.1747-0285.2008.00647.x – ident: e_1_3_2_42_2 doi: 10.1128/AAC.01540-10 – ident: e_1_3_2_22_2 doi: 10.1016/S0021-9258(19)50290-3 – ident: e_1_3_2_6_2 doi: 10.1002/(SICI)1097-0134(199601)24:1<51::AID-PROT4>3.0.CO;2-R – ident: e_1_3_2_15_2 doi: 10.1016/j.jviromet.2007.05.009 – ident: e_1_3_2_34_2 doi: 10.1128/AAC.49.9.3825-3832.2005 – ident: e_1_3_2_40_2 doi: 10.1021/bi2018317 – ident: e_1_3_2_21_2 doi: 10.1128/JVI.78.22.12446-12454.2004 – volume-title: Abstr. Sixth Conf. Retroviruses Opportunistic Infect. year: 1999 ident: e_1_3_2_13_2 contributor: fullname: Tisdale M – ident: e_1_3_2_41_2 doi: 10.1021/ct9004678 – ident: e_1_3_2_11_2 doi: 10.1128/AAC.44.8.2093-2099.2000 – ident: e_1_3_2_43_2 doi: 10.1016/S0969-2126(02)00720-7 – ident: e_1_3_2_17_2 doi: 10.1086/386291 – ident: e_1_3_2_4_2 doi: 10.1007/978-1-4757-9209-6_30 – volume: 12 start-page: S141 year: 2007 ident: e_1_3_2_14_2 article-title: Unraveling the complex resistance pathways of darunavir using the bioinformatics resistance determination (BIRD) publication-title: Antivir. Ther. contributor: fullname: Van Marck H – ident: e_1_3_2_10_2 doi: 10.1128/JVI.78.21.12012-12021.2004 – ident: e_1_3_2_24_2 doi: 10.1016/S0076-6879(97)76066-X – volume-title: Human retroviruses, cancer and AIDS: approaches to prevention and therapy. year: 1988 ident: e_1_3_2_7_2 contributor: fullname: Henderson LE – ident: e_1_3_2_27_2 doi: 10.1107/S0907444906005270 – ident: e_1_3_2_23_2 doi: 10.1110/ps.25502 – ident: e_1_3_2_29_2 doi: 10.1107/S0907444904019158 – ident: e_1_3_2_3_2 doi: 10.1038/374569a0 – ident: e_1_3_2_20_2 doi: 10.1021/jp2074804 – volume-title: The PyMol molecular graphics system. year: 2002 ident: e_1_3_2_30_2 contributor: fullname: DeLano WL – ident: e_1_3_2_36_2 doi: 10.1111/j.1742-4658.2010.07771.x
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SubjectTerms	Anti-HIV Agents - pharmacology Atazanavir Sulfate Carbamates - pharmacology Crystallography, X-Ray Darunavir Drug Resistance, Viral HIV Protease - chemistry HIV Protease - genetics HIV-1 - drug effects HIV-1 - genetics Humans Kinetics Models, Molecular Mutant Proteins - chemistry Mutant Proteins - genetics Mutation, Missense Oligopeptides - pharmacology Point Mutation Protein Binding Protein Conformation Pyridines - pharmacology Sulfonamides - pharmacology Thermodynamics Vaccines and Antiviral Agents
Title	Structural and Thermodynamic Basis of Amprenavir/Darunavir and Atazanavir Resistance in HIV-1 Protease with Mutations at Residue 50
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