7ke0: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(One intermediate revision by the same user not shown)
Line 3: Line 3:
<StructureSection load='7ke0' size='340' side='right'caption='[[7ke0]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
<StructureSection load='7ke0' size='340' side='right'caption='[[7ke0]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7ke0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KE0 FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KE0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WBV:(2S)-tert-butoxy{4-(4-chlorophenyl)-2,3,6-trimethyl-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}acetic+acid'>WBV</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.19&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene>, <scene name='pdbligand=WBV:(2S)-tert-butoxy{4-(4-chlorophenyl)-2,3,6-trimethyl-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}acetic+acid'>WBV</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></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=7ke0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ke0 OCA], [https://pdbe.org/7ke0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ke0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ke0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ke0 ProSAT]</span></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=7ke0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ke0 OCA], [https://pdbe.org/7ke0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ke0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ke0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ke0 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a &gt;24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction. Consequently, STP0404 inhibits proper localization of HIV-1 RNA genomes in viral particles during viral maturation. Y99H and A128T mutations at the LEDGF/p75 binding pocket render resistance to STP0404. Extensive in vivo pharmacological and toxicity investigations demonstrate that STP0404 harbors outstanding therapeutic and safety properties. Overall, STP0404 is a potent and first-in-class ALLINI that targets LEDGF/p75 binding site and has advanced to a human trial.


A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site.,Maehigashi T, Ahn S, Kim UI, Lindenberger J, Oo A, Koneru PC, Mahboubi B, Engelman AN, Kvaratskhelia M, Kim K, Kim B PLoS Pathog. 2021 Jul 22;17(7):e1009671. doi: 10.1371/journal.ppat.1009671., eCollection 2021 Jul. PMID:34293041<ref>PMID:34293041</ref>
==See Also==
 
*[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ke0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: RNA-directed DNA polymerase]]
[[Category: Kvaratskhelia M]]
[[Category: Kvaratskhelia, M]]
[[Category: Lindenberger JJ]]
[[Category: Lindenberger, J J]]
[[Category: Hiv]]
[[Category: Inhibitor]]
[[Category: Integrase]]
[[Category: Transferase-inhibitor complex]]

Latest revision as of 16:38, 6 November 2024

HIV-1 Integrase catalytic core domain complexed with allosteric inhibitor STP03-0404HIV-1 Integrase catalytic core domain complexed with allosteric inhibitor STP03-0404

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.19Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

See Also

7ke0, resolution 2.19Å

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=7ke0&oldid=4228450"