2hah

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:54, 30 August 2023) (edit) (undo)
 
(19 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2hah.jpg|left|200px]]<br /><applet load="2hah" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="2hah, resolution 1.700&Aring;" />
 
-
'''The structure of FIV 12S protease in complex with TL-3'''<br />
 
-
==Overview==
+
==The structure of FIV 12S protease in complex with TL-3==
-
We have obtained the 1.7 A crystal structure of FIV protease (PR) in which, 12 critical residues around the active site have been substituted with the, structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR, was crystallized in complex with the broad-based inhibitor TL-3, which, inhibits wild type FIV and HIV PRs, as well as 12X FIV PR and several, drug-resistant HIV mutants 1234. Biochemical analyses have demonstrated, that TL-3 inhibits these PRs in the order HIV PR &gt; 12X FIV PR &gt; FIV PR, with Ki values of 1.5 nM, 10 nM, and 41 nM, respectively 234. Comparison, of the crystal structures of the TL-3 complexes of 12X FIV and, wild-typeFIV PR revealed theformation of additinal van der Waals, interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR, retained the hydrogen bonding interactions between residues in the flap, regions and active site involving the enzyme and the TL-3 inhibitor in, comparison to both FIV PR and HIV PR. However, the flap regions of the 12X, FIV PR more closely resemble those of HIV PR, having gained several, stabilizing intra-flap interactions not present in wild type FIV PR. These, findings offer a structural explanation for the observed, inhibitor/substrate binding properties of the chimeric PR.
+
<StructureSection load='2hah' size='340' side='right'caption='[[2hah]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2hah]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Feline_immunodeficiency_virus_(isolate_Petaluma) Feline immunodeficiency virus (isolate Petaluma)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HAH 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]] 1.7&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3TL:BENZYL+[(1S,4S,7S,8R,9R,10S,13S,16S)-7,10-DIBENZYL-8,9-DIHYDROXY-1,16-DIMETHYL-4,13-BIS(1-METHYLETHYL)-2,5,12,15,18-PENTAOXO-20-PHENYL-19-OXA-3,6,11,14,17-PENTAAZAICOS-1-YL]CARBAMATE'>3TL</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=2hah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hah OCA], [https://pdbe.org/2hah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hah RCSB], [https://www.ebi.ac.uk/pdbsum/2hah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hah 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/ha/2hah_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=2hah ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
We have obtained the 1.7 A crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV and HIV PRs, as well as 12X FIV PR and several drug-resistant HIV mutants 1234. Biochemical analyses have demonstrated that TL-3 inhibits these PRs in the order HIV PR &gt; 12X FIV PR &gt; FIV PR, with Ki values of 1.5 nM, 10 nM, and 41 nM, respectively 234. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-typeFIV PR revealed theformation of additinal van der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR retained the hydrogen bonding interactions between residues in the flap regions and active site involving the enzyme and the TL-3 inhibitor in comparison to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more closely resemble those of HIV PR, having gained several stabilizing intra-flap interactions not present in wild type FIV PR. These findings offer a structural explanation for the observed inhibitor/substrate binding properties of the chimeric PR.
-
==About this Structure==
+
Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3.,Heaslet H, Lin YC, Tam K, Torbett BE, Elder JH, Stout CD Retrovirology. 2007 Jan 9;4:1. PMID:17212810<ref>PMID:17212810</ref>
-
2HAH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Feline_immunodeficiency_virus Feline immunodeficiency virus] with <scene name='pdbligand=INT:'>INT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAH OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3., Heaslet H, Lin YC, Tam K, Torbett BE, Elder JH, Stout CD, Retrovirology. 2007 Jan 9;4:1. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17212810 17212810]
+
</div>
-
[[Category: Feline immunodeficiency virus]]
+
<div class="pdbe-citations 2hah" style="background-color:#fffaf0;"></div>
-
[[Category: HIV-1 retropepsin]]
+
-
[[Category: Single protein]]
+
-
[[Category: Elder, J.H.]]
+
-
[[Category: Heaslet, H.]]
+
-
[[Category: Lin, Y.C.]]
+
-
[[Category: Stout, C.D.]]
+
-
[[Category: INT]]
+
-
[[Category: aspartyl]]
+
-
[[Category: feline]]
+
-
[[Category: protease]]
+
-
[[Category: retroviral]]
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:30:49 2008''
+
==See Also==
 +
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
 +
[[Category: Elder JH]]
 +
[[Category: Heaslet H]]
 +
[[Category: Lin YC]]
 +
[[Category: Stout CD]]

Current revision

The structure of FIV 12S protease in complex with TL-3

PDB ID 2hah

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hah"
Personal tools