2hs2: Difference between revisions

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[[Image:2hs2.gif|left|200px]]


{{Structure
==Crystal structure of M46L mutant of HIV-1 protease complexed with TMC114 (darunavir)==
|PDB= 2hs2 |SIZE=350|CAPTION= <scene name='initialview01'>2hs2</scene>, resolution 1.22&Aring;
<StructureSection load='2hs2' size='340' side='right'caption='[[2hs2]], [[Resolution|resolution]] 1.22&Aring;' scene=''>
|SITE=
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene> and <scene name='pdbligand=DMS:DIMETHYL SULFOXIDE'>DMS</scene>
<table><tr><td colspan='2'>[[2hs2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HS2 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.22&#8491;</td></tr>
|GENE= GAG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hs2 OCA], [https://pdbe.org/2hs2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hs2 RCSB], [https://www.ebi.ac.uk/pdbsum/2hs2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hs2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q7SSI0_9HIV1 Q7SSI0_9HIV1]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hs/2hs2_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hs2 ConSurf].
<div style="clear:both"></div>


'''Crystal structure of M46L mutant of HIV-1 protease complexed with TMC114 (darunavir)'''
==See Also==
 
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
 
__TOC__
==Overview==
</StructureSection>
TMC114 (darunavir) is a promising clinical inhibitor of HIV-1 protease (PR) for treatment of drug resistant HIV/AIDS. We report the ultra-high 0.84 A resolution crystal structure of the TMC114 complex with PR containing the drug-resistant mutation V32I (PR(V32I)), and the 1.22 A resolution structure of a complex with PR(M46L). These structures show TMC114 bound at two distinct sites, one in the active-site cavity and the second on the surface of one of the flexible flaps in the PR dimer. Remarkably, TMC114 binds at these two sites simultaneously in two diastereomers related by inversion of the sulfonamide nitrogen. Moreover, the flap site is shaped to accommodate the diastereomer with the S-enantiomeric nitrogen rather than the one with the R-enantiomeric nitrogen. The existence of the second binding site and two diastereomers suggest a mechanism for the high effectiveness of TMC114 on drug-resistant HIV and the potential design of new inhibitors.
 
==About this Structure==
2HS2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HS2 OCA].
 
==Reference==
Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114., Kovalevsky AY, Liu F, Leshchenko S, Ghosh AK, Louis JM, Harrison RW, Weber IT, J Mol Biol. 2006 Oct 13;363(1):161-73. Epub 2006 Aug 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16962136 16962136]
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Kovalevsky, A Y.]]
[[Category: Kovalevsky AY]]
[[Category: Liu, F.]]
[[Category: Liu F]]
[[Category: Weber, I T.]]
[[Category: Weber IT]]
[[Category: 017]]
[[Category: CL]]
[[Category: DMS]]
[[Category: aspartic protease active site surface binding site]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:20:54 2008''

Latest revision as of 12:34, 14 February 2024

Crystal structure of M46L mutant of HIV-1 protease complexed with TMC114 (darunavir)Crystal structure of M46L mutant of HIV-1 protease complexed with TMC114 (darunavir)

Structural highlights

2hs2 is a 2 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.22Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q7SSI0_9HIV1

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2hs2, resolution 1.22Å

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

OCA
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