2i4u: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(10 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2i4u.jpg|left|200px]]


<!--
==HIV-1 protease with TMC-126==
The line below this paragraph, containing "STRUCTURE_2i4u", creates the "Structure Box" on the page.
<StructureSection load='2i4u' size='340' side='right'caption='[[2i4u]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2i4u]] 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=2I4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I4U FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DJR:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL+[(1S,2R)-1-BENZYL-2-HYDROXY-3-{ISOBUTYL[(4-METHOXYPHENYL)SULFONYL]AMINO}PROPYL]CARBAMATE'>DJR</scene></td></tr>
{{STRUCTURE_2i4u|  PDB=2i4u  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2i4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i4u OCA], [https://pdbe.org/2i4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i4u RCSB], [https://www.ebi.ac.uk/pdbsum/2i4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i4u ProSAT]</span></td></tr>
 
</table>
'''HIV-1 protease with TMC-126'''
== Function ==
 
[https://www.uniprot.org/uniprot/Q7SSI0_9HIV1 Q7SSI0_9HIV1]
 
== Evolutionary Conservation ==
==Overview==
[[Image:Consurf_key_small.gif|200px|right]]
The introduction of human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) markedly improved the clinical outcome and control of HIV-1 infection. However, cross-resistance among PIs due to a wide spectrum of mutations in viral protease is a major factor limiting their broader clinical use. Here we report on the suppression of PI resistance using a covalent attachment of a phosphonic acid motif to a peptidomimetic inhibitor scaffold. The resulting phosphonate analogs maintain high binding affinity to HIV-1 protease, potent antiretroviral activity, and unlike the parent molecules, display no loss of potency against a panel of clinically important PI-resistant HIV-1 strains. As shown by crystallographic analysis, the phosphonate moiety is highly exposed to solvent with no discernable interactions with any of the enzyme active site or surface residues. We term this effect "solvent anchoring" and demonstrate that it is driven by a favorable change in the inhibitor binding entropy upon the interaction with mutant enzymes. This type of thermodynamic behavior, which was not found with the parent scaffold fully buried in the enzyme active site, is a result of the increased degeneracy of inhibitor binding states, allowing effective molecular adaptation to the expanded cavity volume of mutant proteases. This strategy, which is applicable to various PI scaffolds, should facilitate the design of novel PIs and potentially other antiviral therapeutics.
Check<jmol>
 
  <jmolCheckbox>
==About this Structure==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i4/2i4u_consurf.spt"</scriptWhenChecked>
2I4U 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=2I4U OCA].  
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 
    <text>to colour the structure by Evolutionary Conservation</text>
==Reference==
  </jmolCheckbox>
Suppression of HIV-1 protease inhibitor resistance by phosphonate-mediated solvent anchoring., Cihlar T, He GX, Liu X, Chen JM, Hatada M, Swaminathan S, McDermott MJ, Yang ZY, Mulato AS, Chen X, Leavitt SA, Stray KM, Lee WA, J Mol Biol. 2006 Oct 27;363(3):635-47. Epub 2006 Aug 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16979654 16979654]
</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=2i4u ConSurf].
[[Category: HIV-1 retropepsin]]
<div style="clear:both"></div>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Hatada, M.]]
[[Category: Hatada M]]
[[Category: Hydrolase]]
[[Category: Protein inhibitor complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 07:04:18 2008''

Latest revision as of 12:01, 21 February 2024

HIV-1 protease with TMC-126HIV-1 protease with TMC-126

Structural highlights

2i4u 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 1.5Å
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.

2i4u, resolution 1.50Å

Drag the structure with the mouse to rotate

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

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=2i4u&oldid=4061932"