2az8: Difference between revisions

Revision as of 19:39, 3 May 2008

HIV-1 Protease NL4-3 in complex with inhibitor, TL-3

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

2AZ8 is a Single protein structure of sequence from Human immunodeficiency virus 1. 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 Page seeded by OCA on Sat May 3 19:39:13 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2az8.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2az8 |SIZE=350|CAPTION= <scene name='initialview01'>2az8</scene>, resolution 2.00&Aring;
+The line below this paragraph, containing "STRUCTURE_2az8", creates the "Structure Box" on the page.
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+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])
+-->
-|DOMAIN=
+{{STRUCTURE_2az8|  PDB=2az8  |  SCENE=  }}
-|RELATEDENTRY=[[2az9|2AZ9]], [[2azb|2AZB]], [[2azc|2AZC]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2az8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2az8 OCA], [http://www.ebi.ac.uk/pdbsum/2az8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2az8 RCSB]</span>
-}}
 '''HIV-1 Protease NL4-3 in complex with inhibitor, TL-3'''
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 [[Category: Stout, C D.]]
 [[Category: Torbett, B E.]]
-[[Category: hiv-1]]
+[[Category: Hiv-1]]
-[[Category: inhibitor]]
+[[Category: Inhibitor]]
-[[Category: protease]]
+[[Category: Protease]]
-[[Category: tl-3]]
+[[Category: Tl-3]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 19:39:13 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:59:19 2008''