2azc: Difference between revisions
New page: left|200px<br /> <applet load="2azc" size="450" color="white" frame="true" align="right" spinBox="true" caption="2azc, resolution 2.01Å" /> '''HIV-1 Protease NL4-... |
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[[Image:2azc.gif|left|200px]]<br /> | [[Image:2azc.gif|left|200px]]<br /><applet load="2azc" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2azc" size=" | |||
caption="2azc, resolution 2.01Å" /> | caption="2azc, resolution 2.01Å" /> | ||
'''HIV-1 Protease NL4-3 6X mutant'''<br /> | '''HIV-1 Protease NL4-3 6X mutant'''<br /> | ||
==Overview== | ==Overview== | ||
The development of resistance to anti-retroviral drugs targeted against | The development of resistance to anti-retroviral drugs targeted against HIV is an increasing clinical problem in the treatment of HIV-1-infected individuals. Many patients develop drug-resistant strains of the virus after treatment with inhibitor cocktails (HAART therapy), which include multiple protease inhibitors. Therefore, it is imperative that we understand the mechanisms by which the viral proteins, in particular HIV-1 protease, develop resistance. We have determined the three-dimensional structure of HIV-1 protease NL4-3 in complex with the potent protease inhibitor TL-3 at 2.0 A resolution. We have also obtained the crystal structures of three mutant forms of NL4-3 protease containing one (V82A), three (V82A, M46I, F53L) and six (V82A, M46I, F53L, V77I, L24I, L63P) point mutations in complex with TL-3. The three protease mutants arose sequentially under ex vivo selective pressure in the presence of TL-3, and exhibit fourfold, 11-fold, and 30-fold resistance to TL-3, respectively. This series of protease crystal structures offers insights into the biochemical and structural mechanisms by which the enzyme can overcome inhibition by TL-3 while recovering some of its native catalytic activity. | ||
==About this Structure== | ==About this Structure== | ||
2AZC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http:// | 2AZC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AZC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Elder, J | [[Category: Elder, J H.]] | ||
[[Category: Heaslet, H.]] | [[Category: Heaslet, H.]] | ||
[[Category: Kutilek, V.]] | [[Category: Kutilek, V.]] | ||
[[Category: Lin, Y-C.]] | [[Category: Lin, Y-C.]] | ||
[[Category: Morris, G | [[Category: Morris, G M.]] | ||
[[Category: Stout, C | [[Category: Stout, C D.]] | ||
[[Category: Torbett, B | [[Category: Torbett, B E.]] | ||
[[Category: hiv; protease; inhibitor; tl-3; 6x]] | [[Category: hiv; protease; inhibitor; tl-3; 6x]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:35 2008'' | ||
Revision as of 17:32, 21 February 2008
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HIV-1 Protease NL4-3 6X mutant
OverviewOverview
The development of resistance to anti-retroviral drugs targeted against HIV is an increasing clinical problem in the treatment of HIV-1-infected individuals. Many patients develop drug-resistant strains of the virus after treatment with inhibitor cocktails (HAART therapy), which include multiple protease inhibitors. Therefore, it is imperative that we understand the mechanisms by which the viral proteins, in particular HIV-1 protease, develop resistance. We have determined the three-dimensional structure of HIV-1 protease NL4-3 in complex with the potent protease inhibitor TL-3 at 2.0 A resolution. We have also obtained the crystal structures of three mutant forms of NL4-3 protease containing one (V82A), three (V82A, M46I, F53L) and six (V82A, M46I, F53L, V77I, L24I, L63P) point mutations in complex with TL-3. The three protease mutants arose sequentially under ex vivo selective pressure in the presence of TL-3, and exhibit fourfold, 11-fold, and 30-fold resistance to TL-3, respectively. This series of protease crystal structures offers insights into the biochemical and structural mechanisms by which the enzyme can overcome inhibition by TL-3 while recovering some of its native catalytic activity.
About this StructureAbout this Structure
2AZC is a Single protein structure of sequence from Human immunodeficiency virus 1. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
ReferenceReference
Structural insights into the mechanisms of drug resistance in HIV-1 protease NL4-3., Heaslet H, Kutilek V, Morris GM, Lin YC, Elder JH, Torbett BE, Stout CD, J Mol Biol. 2006 Mar 3;356(4):967-81. Epub 2005 Dec 20. PMID:16403521
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