2qnp: Difference between revisions

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[[Image:2qnp.png|left|200px]]
==HIV-1 Protease in complex with a iodo decorated pyrrolidine-based inhibitor==
<StructureSection load='2qnp' size='340' side='right' caption='[[2qnp]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2qnp]] is a 2 chain structure with 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=2QNP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QNP FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=QN2:N,N-(3S,4S)-PYRROLIDINE-3,4-DIYLBIS[N-(4-IODOBENZYL)BENZENESULFONAMIDE]'>QN2</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2pqz|2pqz]], [[2pwc|2pwc]], [[2pwr|2pwr]], [[2qnn|2qnn]], [[2qnq|2qnq]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qnp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qnp RCSB], [http://www.ebi.ac.uk/pdbsum/2qnp PDBsum]</span></td></tr>
<table>
== 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/qn/2qnp_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Infections with the human immunodeficiency virus, which inevitably lead to the development of AIDS, are still among the most serious global health problems causing more than 2.5 million deaths per year. In the pathophysiological processes of this pandemic, HIV protease has proven to be an invaluable drug target because of its essential role in the virus' replication process. By use of pyrrolidine as core structure, symmetric 3,4-bis- N-alkylsulfonamides were designed and synthesized enantioselectively from d-(-)-tartaric acid as a new class of HIV protease inhibitors. Structure-guided design using the cocrystal structure of an initial lead as starting point resulted in a second series of inhibitors with improved affinity. The binding modes of four representatives were determined by X-ray crystallography to elucidate the underlying factors accounting for the SAR. With this information for further rational design, the combination of suitable side chains resulted in a final inhibitor showing a significantly improved affinity of K i = 74 nM.


{{STRUCTURE_2qnp|  PDB=2qnp  |  SCENE=  }}
Structure-Guided Design of C2-Symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold.,Blum A, Bottcher J, Heine A, Klebe G, Diederich WE J Med Chem. 2008 Apr 10;51(7):2078-87. Epub 2008 Mar 19. PMID:18348517<ref>PMID:18348517</ref>


===HIV-1 Protease in complex with a iodo decorated pyrrolidine-based inhibitor===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_18348517}}
== References ==
 
<references/>
==About this Structure==
__TOC__
[[2qnp]] is a 2 chain structure with 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=2QNP OCA].
</StructureSection>
 
==Reference==
<ref group="xtra">PMID:018348517</ref><references group="xtra"/>
[[Category: HIV-1 retropepsin]]
[[Category: HIV-1 retropepsin]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]

Revision as of 21:24, 30 September 2014

HIV-1 Protease in complex with a iodo decorated pyrrolidine-based inhibitorHIV-1 Protease in complex with a iodo decorated pyrrolidine-based inhibitor

Structural highlights

2qnp 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.
Ligands:,
Related:2pqz, 2pwc, 2pwr, 2qnn, 2qnq
Gene:gag-pol (Human immunodeficiency virus 1)
Activity:HIV-1 retropepsin, with EC number 3.4.23.16
Resources:FirstGlance, OCA, RCSB, PDBsum

Evolutionary Conservation

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

Publication Abstract from PubMed

Infections with the human immunodeficiency virus, which inevitably lead to the development of AIDS, are still among the most serious global health problems causing more than 2.5 million deaths per year. In the pathophysiological processes of this pandemic, HIV protease has proven to be an invaluable drug target because of its essential role in the virus' replication process. By use of pyrrolidine as core structure, symmetric 3,4-bis- N-alkylsulfonamides were designed and synthesized enantioselectively from d-(-)-tartaric acid as a new class of HIV protease inhibitors. Structure-guided design using the cocrystal structure of an initial lead as starting point resulted in a second series of inhibitors with improved affinity. The binding modes of four representatives were determined by X-ray crystallography to elucidate the underlying factors accounting for the SAR. With this information for further rational design, the combination of suitable side chains resulted in a final inhibitor showing a significantly improved affinity of K i = 74 nM.

Structure-Guided Design of C2-Symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold.,Blum A, Bottcher J, Heine A, Klebe G, Diederich WE J Med Chem. 2008 Apr 10;51(7):2078-87. Epub 2008 Mar 19. PMID:18348517[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Blum A, Bottcher J, Heine A, Klebe G, Diederich WE. Structure-Guided Design of C2-Symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold. J Med Chem. 2008 Apr 10;51(7):2078-87. Epub 2008 Mar 19. PMID:18348517 doi:10.1021/jm701142s

2qnp, resolution 1.41Å

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OCA
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