2q54: Difference between revisions

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[[Image:2q54.jpg|left|200px]]<br /><applet load="2q54" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2q54, resolution 1.85&Aring;" />
'''Crystal structure of KB73 bound to HIV-1 protease'''<br />


==Overview==
==Crystal structure of KB73 bound to HIV-1 protease==
A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure-activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.
<StructureSection load='2q54' size='340' side='right'caption='[[2q54]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2q54]] 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=2Q54 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q54 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MU1:N~2~-ACETYL-N-[(1S,3S,4S)-4-({[(5S)-3-(3-ACETYLPHENYL)-2-OXO-1,3-OXAZOLIDIN-5-YL]CARBONYL}AMINO)-1-BENZYL-3-HYDROXY-5-PHENYLPENTYL]-L-VALINAMIDE'>MU1</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=2q54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q54 OCA], [https://pdbe.org/2q54 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q54 RCSB], [https://www.ebi.ac.uk/pdbsum/2q54 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q54 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O38710_9HIV1 O38710_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/q5/2q54_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=2q54 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2Q54 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] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=ACT:'>ACT</scene> and <scene name='pdbligand=MU1:'>MU1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q54 OCA].
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres., Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM, J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17696512 17696512]
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Nalam, M N.L.]]
[[Category: Nalam MNL]]
[[Category: Schiffer, C A.]]
[[Category: Schiffer CA]]
[[Category: ACT]]
[[Category: MU1]]
[[Category: PO4]]
[[Category: drug design]]
[[Category: hiv-1 protease]]
[[Category: hydrolase]]
[[Category: protease inhibitors]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:36:06 2008''

Latest revision as of 16:53, 13 March 2024

Crystal structure of KB73 bound to HIV-1 proteaseCrystal structure of KB73 bound to HIV-1 protease

Structural highlights

2q54 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 1.85Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

O38710_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

2q54, resolution 1.85Å

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