Drug Resistance Mutations Alter Dynamics of Inhibitor-Bound HIV-1 Protease
Identifieur interne : 003416 ( Main/Merge ); précédent : 003415; suivant : 003417Drug Resistance Mutations Alter Dynamics of Inhibitor-Bound HIV-1 Protease
Auteurs : Yufeng Cai [États-Unis] ; Wazo Myint [États-Unis] ; Janet L. Paulsen [États-Unis] ; Celia A. Schiffer [États-Unis] ; Rieko Ishima [États-Unis] ; Nese Kurt Yilmaz [États-Unis]Source :
- Journal of Chemical Theory and Computation [ 1549-9618 ] ; 2014.
Abstract
Under the selective pressure of therapy,
HIV-1 protease mutants
resistant to inhibitors evolve to confer drug resistance. Such mutations
can impact both the dynamics and structures of the bound and unbound
forms of the enzyme. Flap+ is a multidrug-resistant variant of HIV-1
protease with a combination of primary and secondary resistance mutations
(L10I, G48V, I54V, V82A) and a strikingly altered thermodynamic profile
for darunavir (DRV) binding relative to the wild-type protease. We
elucidated the impact of these mutations on protein dynamics in the
DRV-bound state using molecular dynamics simulations and NMR relaxation
experiments. Both methods concur in that the conformational ensemble
and dynamics of protease are impacted by the drug resistance mutations
in Flap+ variant. Surprisingly this change in ensemble dynamics is
different from that observed in the unliganded form of the same variant
(Cai, Y. et al.
Url:
DOI: 10.1021/ct4010454
PubMed: 25136270
PubMed Central: 4132871
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Paulsen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Biochemistry and Molecular Pharmacology,<institution>University of Massachusetts Medical School</institution>, Worcester, Massachusetts 01605,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Schiffer, Celia A" sort="Schiffer, Celia A" uniqKey="Schiffer C" first="Celia A." last="Schiffer">Celia A. Schiffer</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Biochemistry and Molecular Pharmacology,<institution>University of Massachusetts Medical School</institution>, Worcester, Massachusetts 01605,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ishima, Rieko" sort="Ishima, Rieko" uniqKey="Ishima R" first="Rieko" last="Ishima">Rieko Ishima</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Structural Biology, School of Medicine,<institution>University of Pittsburgh Biomedical Science Tower 3</institution>, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15260,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kurt Yilmaz, Nese" sort="Kurt Yilmaz, Nese" uniqKey="Kurt Yilmaz N" first="Nese" last="Kurt Yilmaz">Nese Kurt Yilmaz</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Biochemistry and Molecular Pharmacology,<institution>University of Massachusetts Medical School</institution>, Worcester, Massachusetts 01605,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Chemical Theory and Computation</title><idno type="ISSN">1549-9618</idno><idno type="eISSN">1549-9626</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="ct-2013-010454_0006" id="ab-tgr1"></graphic></p><p>Under the selective pressure of therapy,
HIV-1 protease mutants
resistant to inhibitors evolve to confer drug resistance. Such mutations
can impact both the dynamics and structures of the bound and unbound
forms of the enzyme. Flap+ is a multidrug-resistant variant of HIV-1
protease with a combination of primary and secondary resistance mutations
(L10I, G48V, I54V, V82A) and a strikingly altered thermodynamic profile
for darunavir (DRV) binding relative to the wild-type protease. We
elucidated the impact of these mutations on protein dynamics in the
DRV-bound state using molecular dynamics simulations and NMR relaxation
experiments. Both methods concur in that the conformational ensemble
and dynamics of protease are impacted by the drug resistance mutations
in Flap+ variant. Surprisingly this change in ensemble dynamics is
different from that observed in the unliganded form of the same variant
(Cai, Y. et al. <italic>J. Chem. Theory Comput.</italic><bold>2012</bold>, <italic>8</italic>, 3452–3462). Our comparative
analysis of both inhibitor-free and bound states presents a comprehensive
picture of the altered dynamics in drug-resistant mutant HIV-1 protease
and underlies the importance of incorporating dynamic analysis of
the whole system, including the unliganded state, into revealing drug
resistance mechanisms.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Altman, M D" uniqKey="Altman M">M. D. Altman</name></author><author><name sortKey="Ali, A" uniqKey="Ali A">A. Ali</name></author><author><name sortKey="Reddy, G S" uniqKey="Reddy G">G. S. Reddy</name></author><author><name sortKey="Nalam, M N" uniqKey="Nalam M">M. N. Nalam</name></author><author><name sortKey="Anjum, S G" uniqKey="Anjum S">S. G. Anjum</name></author><author><name sortKey="Cao, H" uniqKey="Cao H">H. Cao</name></author><author><name sortKey="Chellappan, S" uniqKey="Chellappan S">S. Chellappan</name></author><author><name sortKey="Kairys, V" uniqKey="Kairys V">V. Kairys</name></author><author><name sortKey="Fernandes, M X" uniqKey="Fernandes M">M. X. Fernandes</name></author><author><name sortKey="Gilson, M K" uniqKey="Gilson M">M. K. Gilson</name></author><author><name sortKey="Schiffer, C A" uniqKey="Schiffer C">C. A. Schiffer</name></author><author><name sortKey="Rana, T M" uniqKey="Rana T">T. M. Rana</name></author><author><name sortKey="Tidor, B" uniqKey="Tidor B">B. Tidor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Foulkes Murzycki, J E" uniqKey="Foulkes Murzycki J">J. E. Foulkes-Murzycki</name></author><author><name sortKey="Rosi, C" uniqKey="Rosi C">C. Rosi</name></author><author><name sortKey="Kurt Yilmaz, N" uniqKey="Kurt Yilmaz N">N. Kurt Yilmaz</name></author><author><name sortKey="Shafer, R W" uniqKey="Shafer R">R. W. Shafer</name></author><author><name sortKey="Schiffer, C A" uniqKey="Schiffer C">C. A. Schiffer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clemente, J C" uniqKey="Clemente J">J. C. Clemente</name></author><author><name sortKey="Hemrajani, R" uniqKey="Hemrajani R">R. Hemrajani</name></author><author><name sortKey="Blum, L E" uniqKey="Blum L">L. E. Blum</name></author><author><name sortKey="Goodenow, M M" uniqKey="Goodenow M">M. M. Goodenow</name></author><author><name sortKey="Dunn, B M" uniqKey="Dunn B">B. M. Dunn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Foulkes Murzycki, J E" uniqKey="Foulkes Murzycki J">J. E. Foulkes-Murzycki</name></author><author><name sortKey="Scott, W R" uniqKey="Scott W">W. R. Scott</name></author><author><name sortKey="Schiffer, C A" uniqKey="Schiffer C">C. A. Schiffer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Freedberg, D I" uniqKey="Freedberg D">D. I. Freedberg</name></author><author><name sortKey="Ishima, R" uniqKey="Ishima R">R. Ishima</name></author><author><name sortKey="Jacob, J" uniqKey="Jacob J">J. Jacob</name></author><author><name sortKey="Wang, Y X" uniqKey="Wang Y">Y. X. Wang</name></author><author><name sortKey="Kustanovich, I" uniqKey="Kustanovich I">I. Kustanovich</name></author><author><name sortKey="Louis, J M" uniqKey="Louis J">J. M. Louis</name></author><author><name sortKey="Torchia, D A" uniqKey="Torchia D">D. A. Torchia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, Y" uniqKey="Cai Y">Y. Cai</name></author><author><name sortKey="Yilmaz, N K" uniqKey="Yilmaz N">N. K. Yilmaz</name></author><author><name sortKey="Myint, W" uniqKey="Myint W">W. Myint</name></author><author><name sortKey="Ishima, R" uniqKey="Ishima R">R. Ishima</name></author><author><name sortKey="Schiffer, C A" uniqKey="Schiffer C">C. A. Schiffer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shafer, R W" uniqKey="Shafer R">R. W. Shafer</name></author><author><name sortKey="Stevenson, D" uniqKey="Stevenson D">D. Stevenson</name></author><author><name sortKey="Chan, B" uniqKey="Chan B">B. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="King, N M" uniqKey="King N">N. M. King</name></author><author><name sortKey="Prabu Jeyabalan, M" uniqKey="Prabu Jeyabalan M">M. Prabu-Jeyabalan</name></author><author><name sortKey="Bandaranayake, R M" uniqKey="Bandaranayake R">R. M. Bandaranayake</name></author><author><name sortKey="Nalam, M N" uniqKey="Nalam M">M. N. Nalam</name></author><author><name sortKey="Ozen, A" uniqKey="Ozen A">A. Ozen</name></author><author><name sortKey="Haliloglu, T" uniqKey="Haliloglu T">T. Haliloglu</name></author><author><name sortKey="Schiffer, C" uniqKey="Schiffer C">C. Schiffer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Case, D A" uniqKey="Case D">D. A. Case</name></author><author><name sortKey="Cheatham, T E" uniqKey="Cheatham T">T. E. Cheatham</name></author><author><name sortKey="Darden, T" uniqKey="Darden T">T. Darden</name></author><author><name sortKey="Gohlke, H" uniqKey="Gohlke H">H. Gohlke</name></author><author><name sortKey="Luo, R" uniqKey="Luo R">R. Luo</name></author><author><name sortKey="Merz, K M" uniqKey="Merz K">K. M. Merz</name></author><author><name sortKey="Onufriev, A" uniqKey="Onufriev A">A. Onufriev</name></author><author><name sortKey="Simmerling, C" uniqKey="Simmerling C">C. Simmerling</name></author><author><name sortKey="Wang, B" uniqKey="Wang B">B. Wang</name></author><author><name sortKey="Woods, R J" uniqKey="Woods R">R. J. Woods</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Surleraux, D L" uniqKey="Surleraux D">D. L. Surleraux</name></author><author><name sortKey="Tahri, A" uniqKey="Tahri A">A. Tahri</name></author><author><name sortKey="Verschueren, W G" uniqKey="Verschueren W">W. G. Verschueren</name></author><author><name sortKey="Pille, G M" uniqKey="Pille G">G. M. Pille</name></author><author><name sortKey="De Kock, H A" uniqKey="De Kock H">H. A. de Kock</name></author><author><name sortKey="Jonckers, T H" uniqKey="Jonckers T">T. H. Jonckers</name></author><author><name sortKey="Peeters, A" uniqKey="Peeters A">A. Peeters</name></author><author><name sortKey="De Meyer, S" uniqKey="De Meyer S">S. De Meyer</name></author><author><name sortKey="Azijn, H" uniqKey="Azijn H">H. Azijn</name></author><author><name sortKey="Pauwels, R" uniqKey="Pauwels R">R. Pauwels</name></author><author><name sortKey="De Bethune, M P" uniqKey="De Bethune M">M. P. de Bethune</name></author><author><name sortKey="King, N M" uniqKey="King N">N. M. King</name></author><author><name sortKey="Prabu Jeyabalan, M" uniqKey="Prabu Jeyabalan M">M. Prabu-Jeyabalan</name></author><author><name sortKey="Schiffer, C A" uniqKey="Schiffer C">C. A. Schiffer</name></author><author><name sortKey="Wigerinck, P B" uniqKey="Wigerinck P">P. B. Wigerinck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Duan, Y" uniqKey="Duan Y">Y. Duan</name></author><author><name sortKey="Wu, C" uniqKey="Wu C">C. Wu</name></author><author><name sortKey="Chowdhury, S" uniqKey="Chowdhury S">S. Chowdhury</name></author><author><name sortKey="Lee, M C" uniqKey="Lee M">M. C. Lee</name></author><author><name sortKey="Xiong, G" uniqKey="Xiong G">G. Xiong</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Yang, R" uniqKey="Yang R">R. Yang</name></author><author><name sortKey="Cieplak, P" uniqKey="Cieplak P">P. Cieplak</name></author><author><name sortKey="Luo, R" uniqKey="Luo R">R. Luo</name></author><author><name sortKey="Lee, T" uniqKey="Lee T">T. Lee</name></author><author><name sortKey="Caldwell, J" uniqKey="Caldwell J">J. Caldwell</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Kollman, P" uniqKey="Kollman P">P. Kollman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ryckaert, J P" uniqKey="Ryckaert J">J.-P. Ryckaert</name></author><author><name sortKey="Ciccotti, G" uniqKey="Ciccotti G">G. Ciccotti</name></author><author><name sortKey="Berendsen, H J C" uniqKey="Berendsen H">H. J. C. Berendsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Humphrey, W" uniqKey="Humphrey W">W. Humphrey</name></author><author><name sortKey="Dalke, A" uniqKey="Dalke A">A. Dalke</name></author><author><name sortKey="Schulten, K" uniqKey="Schulten K">K. Schulten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, L J" uniqKey="Smith L">L. J. Smith</name></author><author><name sortKey="Mark, A E" uniqKey="Mark A">A. E. Mark</name></author><author><name sortKey="Dobson, C M" uniqKey="Dobson C">C. M. Dobson</name></author><author><name sortKey="Vangunsteren, W F" uniqKey="Vangunsteren W">W. F. Vangunsteren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hansen, D F" uniqKey="Hansen D">D. F. Hansen</name></author><author><name sortKey="Vallurupalli, P" uniqKey="Vallurupalli P">P. Vallurupalli</name></author><author><name sortKey="Kay, L E" uniqKey="Kay L">L. E. Kay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jee, J" uniqKey="Jee J">J. Jee</name></author><author><name sortKey="Ishima, R" uniqKey="Ishima R">R. Ishima</name></author><author><name sortKey="Gronenborn, A M" uniqKey="Gronenborn A">A. M. Gronenborn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lipari, G" uniqKey="Lipari G">G. Lipari</name></author><author><name sortKey="Szabo, A" uniqKey="Szabo A">A. Szabo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nicholson, L K" uniqKey="Nicholson L">L. K. Nicholson</name></author><author><name sortKey="Yamazaki, T" uniqKey="Yamazaki T">T. Yamazaki</name></author><author><name sortKey="Torchia, D A" uniqKey="Torchia D">D. A. Torchia</name></author><author><name sortKey="Grzesiek, S" uniqKey="Grzesiek S">S. Grzesiek</name></author><author><name sortKey="Bax, A" uniqKey="Bax A">A. Bax</name></author><author><name sortKey="Stahl, S J" uniqKey="Stahl S">S. J. Stahl</name></author><author><name sortKey="Kaufman, J D" uniqKey="Kaufman J">J. D. Kaufman</name></author><author><name sortKey="Wingfield, P T" uniqKey="Wingfield P">P. T. Wingfield</name></author><author><name sortKey="Lam, P Y" uniqKey="Lam P">P. Y. Lam</name></author><author><name sortKey="Jadhav, P K" uniqKey="Jadhav P">P. K. Jadhav</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Vera, I X0a M" uniqKey="De Vera I">I.
M. de Vera</name></author><author><name sortKey="Blackburn, M E" uniqKey="Blackburn M">M. E. Blackburn</name></author><author><name sortKey="Fanucci, G E" uniqKey="Fanucci G">G. E. Fanucci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tzeng, S R" uniqKey="Tzeng S">S. R. Tzeng</name></author><author><name sortKey="Kalodimos, C G" uniqKey="Kalodimos C">C. G. Kalodimos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perozzo, R" uniqKey="Perozzo R">R. Perozzo</name></author><author><name sortKey="Folkers, G" uniqKey="Folkers G">G. Folkers</name></author><author><name sortKey="Scapozza, L" uniqKey="Scapozza L">L. Scapozza</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, Y" uniqKey="Cai Y">Y. Cai</name></author><author><name sortKey="Schiffer, C A" uniqKey="Schiffer C">C. A. Schiffer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abel, R" uniqKey="Abel R">R. Abel</name></author><author><name sortKey="Salam, N K" uniqKey="Salam N">N. K. Salam</name></author><author><name sortKey="Shelley, J" uniqKey="Shelley J">J. Shelley</name></author><author><name sortKey="Farid, R" uniqKey="Farid R">R. Farid</name></author><author><name sortKey="Friesner, R A" uniqKey="Friesner R">R. A. Friesner</name></author><author><name sortKey="Sherman, W" uniqKey="Sherman W">W. Sherman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fenley, A T" uniqKey="Fenley A">A. T. Fenley</name></author><author><name sortKey="Muddana, H S" uniqKey="Muddana H">H. S. Muddana</name></author><author><name sortKey="Gilson, M K" uniqKey="Gilson M">M. K. Gilson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ozen, A" uniqKey="Ozen A">A. Ozen</name></author><author><name sortKey="Haliloglu, T" uniqKey="Haliloglu T">T. Haliloglu</name></author><author><name sortKey="Schiffer, C A" uniqKey="Schiffer C">C. A. Schiffer</name></author></analytic></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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