5f3t: Difference between revisions
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==Dengue serotype 3 RNA-dependent RNA polymerase bound to JF-31-MG46== | |||
<StructureSection load='5f3t' size='340' side='right' caption='[[5f3t]], [[Resolution|resolution]] 2.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5f3t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F3T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F3T FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5UH:2-(4-METHOXY-3-PHENYL-PHENYL)ETHANOIC+ACID'>5UH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f3z|5f3z]], [[5f41|5f41]]</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=5f3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f3t OCA], [http://pdbe.org/5f3t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f3t RCSB], [http://www.ebi.ac.uk/pdbsum/5f3t PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/Q6DLV0_9FLAV Q6DLV0_9FLAV]] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS000336_004_099774] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We performed a fragment screen on the dengue virus serotype 3 RNA-dependent RNA polymerase using X-ray crystallography. A screen of 1,400 fragments in pools of 8 identified a single hit that bound in a novel pocket in the protein. This pocket is located in the polymerase palm sub-domain and conserved across the four serotypes of dengue virus. The compound binds to the polymerase in solution as evidenced by surface-plasmon resonance and isothermal titration calorimetry analyses. Related compounds where a phenyl is replaced by a thiophene, show higher-affinity binding, indicating the potential for rational design. Importantly, inhibition of enzyme activity correlated with the binding affinity, showing that the pocket is functionally important for polymerase activity. This fragment is an excellent starting point for optimization through rational structure-based design. | |||
A Conserved Pocket in the Dengue Virus Polymerase Identified Through Fragment-Based Screening.,Noble CG, Lim SP, Arora R, Yokokawa F, Nilar S, Seh CC, Wright SK, Benson TE, Smith PW, Shi PY J Biol Chem. 2016 Feb 12. pii: jbc.M115.710731. PMID:26872970<ref>PMID:26872970</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5f3t" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Noble, C G]] | |||
[[Category: Dengue]] | |||
[[Category: Rdrp inhibitor]] | |||
[[Category: Rna-dependent rna polymerase]] | |||
[[Category: Transferase]] | |||
Revision as of 21:07, 26 February 2016
Dengue serotype 3 RNA-dependent RNA polymerase bound to JF-31-MG46Dengue serotype 3 RNA-dependent RNA polymerase bound to JF-31-MG46
Structural highlights
Function[Q6DLV0_9FLAV] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS000336_004_099774] Publication Abstract from PubMedWe performed a fragment screen on the dengue virus serotype 3 RNA-dependent RNA polymerase using X-ray crystallography. A screen of 1,400 fragments in pools of 8 identified a single hit that bound in a novel pocket in the protein. This pocket is located in the polymerase palm sub-domain and conserved across the four serotypes of dengue virus. The compound binds to the polymerase in solution as evidenced by surface-plasmon resonance and isothermal titration calorimetry analyses. Related compounds where a phenyl is replaced by a thiophene, show higher-affinity binding, indicating the potential for rational design. Importantly, inhibition of enzyme activity correlated with the binding affinity, showing that the pocket is functionally important for polymerase activity. This fragment is an excellent starting point for optimization through rational structure-based design. A Conserved Pocket in the Dengue Virus Polymerase Identified Through Fragment-Based Screening.,Noble CG, Lim SP, Arora R, Yokokawa F, Nilar S, Seh CC, Wright SK, Benson TE, Smith PW, Shi PY J Biol Chem. 2016 Feb 12. pii: jbc.M115.710731. PMID:26872970[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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