4nrt: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: '''Unreleased structure''' The entry 4nrt is ON HOLD Authors: Croci, R., Pezzullo, M., Tarantino, D., Mastrangelo, E., Milani, M., Bolognesi, M. Description: Human Norovirus polymerase... |
No edit summary |
||
| (6 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Human Norovirus polymerase bound to Compound 6 (suramin derivative)== | |||
<StructureSection load='4nrt' size='340' side='right'caption='[[4nrt]], [[Resolution|resolution]] 2.02Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4nrt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Norwalk-like_virus Norwalk-like virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NRT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NRT 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]] 2.022Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2NG:4-({4-METHYL-3-[(3-NITROBENZOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,5-DISULFONIC+ACID'>2NG</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=4nrt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nrt OCA], [https://pdbe.org/4nrt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nrt RCSB], [https://www.ebi.ac.uk/pdbsum/4nrt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nrt ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0ZNP5_9CALI A0ZNP5_9CALI] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Noroviruses (NV) are +ssRNA viruses responsible for severe gastroenteritis; no effective vaccines/antivirals are currently available. We previously identified Suramin (9) as a potent inhibitor of NV-RNA dependent RNA polymerase (NV-RdRp). Despite significant in vitro activities versus several pharmacological targets, Suramin clinical use is hampered by pharmacokinetics/toxicity problems. To improve Suramin access to NV-RdRp in vivo, a Suramin-derivative, 8, devoid of two sulphonate groups, was synthesized, achieving significant anti-human-NV-RdRp activity (IC50 = 28 nM); the compound inhibits also murine NV (mNV) RdRp. The synthesis process led to the isolation/characterization of lower molecular weight intermediates (3-7) hosting only one sulphonate head. The crystal structures of both hNV/mNV-RdRps in complex with 6, were analyzed, providing new knowledge on the interactions that a small fragment can establish with NV-RdRps, and establishing a platform for structure-guided optimization of potency, selectivity and drugability. | |||
Structural bases of norovirus RNA dependent RNA polymerase inhibition by novel suramin-related compounds.,Croci R, Pezzullo M, Tarantino D, Milani M, Tsay SC, Sureshbabu R, Tsai YJ, Mastrangelo E, Rohayem J, Bolognesi M, Hwu JR PLoS One. 2014 Mar 12;9(3):e91765. doi: 10.1371/journal.pone.0091765. eCollection, 2014. PMID:24622391<ref>PMID:24622391</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4nrt" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Norwalk-like virus]] | |||
[[Category: Bolognesi M]] | |||
[[Category: Croci R]] | |||
[[Category: Mastrangelo E]] | |||
[[Category: Milani M]] | |||
[[Category: Pezzullo M]] | |||
[[Category: Tarantino D]] | |||
