View source for 4fiv


==FIV PROTEASE COMPLEXED WITH AN INHIBITOR LP-130==
<StructureSection load='4fiv' size='340' side='right'caption='[[4fiv]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4fiv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Feline_immunodeficiency_virus Feline immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FIV 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LP1:4-[2-(2-ACETYLAMINO-3-NAPHTALEN-1-YL-PROPIONYLAMINO)-4-METHYL-PENTANOYLAMINO]-3-HYDROXY-6-METHYL-HEPTANOIC+ACID+[1-(1-CARBAMOYL-2-NAPHTHALEN-1-YL-ETHYLCARBAMOYL)-PROPYL]-AMIDE'>LP1</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=4fiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fiv OCA], [https://pdbe.org/4fiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fiv RCSB], [https://www.ebi.ac.uk/pdbsum/4fiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fiv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q66972_9RETR Q66972_9RETR] 
== 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/fi/4fiv_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=4fiv ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
One of the major problems encountered in antiviral therapy against AIDS is the emergence of viral variants that exhibit drug resistance. The sequences of proteases (PRs) from related retroviruses sometimes include, at structurally equivalent positions, amino acids identical to those found in drug-resistant forms of HIV-1 PR. The statine-based inhibitor LP-130 was found to be a universal, nanomolar-range inhibitor against all tested retroviral PRs. We solved the crystal structures of LP-130 in complex with retroviral PRs from HIV-1, feline immunodeficiency virus, and equine infectious anemia virus and compared the structures to determine the differences in the interactions between the inhibitor and the active-site residues of the enzymes. This comparison shows an extraordinary similarity in the binding modes of the inhibitor molecules. The only exceptions are the different conformations of naphthylalanine side chains at the P3/P3' positions, which might be responsible for the variation in the Ki values. These findings indicate that successful inhibition of different retroviral PRs by LP-130 is achieved because this compound can be accommodated without serious conformational differences, despite the variations in the type of residues forming the active-site region. Although strong, specific interactions between the ligand and the enzyme might improve the potency of the inhibitor, the absence of such interactions seems to favor the universality of the compound. Hence, the ability of potential anti-AIDS drugs to inhibit multiple retroviral PRs might indicate their likelihood of not eliciting drug resistance. These studies may also contribute to the development of a small-animal model for preclinical testing of antiviral compounds.

Toward a universal inhibitor of retroviral proteases: comparative analysis of the interactions of LP-130 complexed with proteases from HIV-1, FIV, and EIAV.,Kervinen J, Lubkowski J, Zdanov A, Bhatt D, Dunn BM, Hui KY, Powell DJ, Kay J, Wlodawer A, Gustchina A Protein Sci. 1998 Nov;7(11):2314-23. PMID:9827997<ref>PMID:9827997</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4fiv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Feline immunodeficiency virus]]
[[Category: Large Structures]]
[[Category: Gustchina A]]
[[Category: Kervinen J]]
[[Category: Lubkowski J]]
[[Category: Wlodawer A]]
[[Category: Zdanov A]]