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==Structure of HIV cleaved synaptic complex (CSC) intasome bound with calcium== | |||
<StructureSection load='6put' size='340' side='right'caption='[[6put]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6put]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PUT FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6put FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6put OCA], [http://pdbe.org/6put PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6put RCSB], [http://www.ebi.ac.uk/pdbsum/6put PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6put ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/DN7D_SACS2 DN7D_SACS2]] Can constrain negative DNA supercoils. May be involved in maintaining the integrity of the genome at high temperature (By similarity). Stimulates the Holliday junction cleavage activity of Hjc (PubMed:11709558).[UniProtKB:P61990]<ref>PMID:11709558</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretrovirals, integrase (IN) strand transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of HIV intasomes bound to the latest generation INSTIs. These structures highlight how small changes in the IN active site can have significant implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals. | |||
Structural basis for strand transfer inhibitor binding to HIV intasomes.,Passos DO, Li M, Jozwik IK, Zhao XZ, Santos-Martins D, Yang R, Smith SJ, Jeon Y, Forli S, Hughes SH, Burke TR Jr, Craigie R, Lyumkis D Science. 2020 Jan 30. pii: science.aay8015. doi: 10.1126/science.aay8015. PMID:32001521<ref>PMID:32001521</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6put" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Jozwik, I K]] | |||
[[Category: Lyumkis, D]] | |||
[[Category: Passos, D]] | |||
[[Category: Enzyme]] | |||
[[Category: Intasome]] | |||
[[Category: Integrase]] | |||
[[Category: Transposition]] | |||
[[Category: Viral protein]] | |||
[[Category: Viral protein-dna complex]] | |||
Revision as of 07:20, 13 February 2020
Structure of HIV cleaved synaptic complex (CSC) intasome bound with calciumStructure of HIV cleaved synaptic complex (CSC) intasome bound with calcium
Structural highlights
Function[DN7D_SACS2] Can constrain negative DNA supercoils. May be involved in maintaining the integrity of the genome at high temperature (By similarity). Stimulates the Holliday junction cleavage activity of Hjc (PubMed:11709558).[UniProtKB:P61990][1] Publication Abstract from PubMedThe HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretrovirals, integrase (IN) strand transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of HIV intasomes bound to the latest generation INSTIs. These structures highlight how small changes in the IN active site can have significant implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals. Structural basis for strand transfer inhibitor binding to HIV intasomes.,Passos DO, Li M, Jozwik IK, Zhao XZ, Santos-Martins D, Yang R, Smith SJ, Jeon Y, Forli S, Hughes SH, Burke TR Jr, Craigie R, Lyumkis D Science. 2020 Jan 30. pii: science.aay8015. doi: 10.1126/science.aay8015. PMID:32001521[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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