3upf - Revision history

OCA at 10:25, 1 March 2024

OCA — Fri, 01 Mar 2024 10:25:42 GMT

←Older revision		Revision as of 10:25, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UPF FirstGlance]. <br>		<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UPF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.6Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nah\|3nah]], [[3nai\|3nai]], [[3uqs\|3uqs]], [[3ur0\|3ur0]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [https://pdbe.org/3upf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [https://www.ebi.ac.uk/pdbsum/3upf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3upf 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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [https://pdbe.org/3upf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [https://www.ebi.ac.uk/pdbsum/3upf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3upf ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/Q80J95_9CALI Q80J95_9CALI]
-	Caliciviridae are RNA viruses with a single-stranded, positively oriented polyadenylated genome, responsible for a broad spectrum of diseases such as acute gastroenteritis in humans. Recently, analyses on the structures and functionalities of the RNA-dependent RNA polymerase (RdRp) from several Caliciviruses have been reported. The RdRp is predicted to play a key role in genome replication, as well as in synthesis and amplification of additional subgenomic RNA. Starting from the crystal structures of human Norovirus (hNV) RdRp, we performed an in silico docking search to identify synthetic compounds with predicted high affinity for the enzyme active site. The best-ranked candidates were tested in vitro on murine Norovirus (MNV) and hNV RdRps to assay their inhibition of RNA polymerization. The results of such combined computational and experimental screening approach led to the identification of two high-potency inhibitors: Suramin and NF023, both symmetric divalent molecules hosting two naphthalene-trisulfonic acid heads. We report here the crystal structure of MNV RdRp alone and in the presence of the two identified inhibitors. Both inhibitory molecules occupy the same RdRp site, between the fingers and thumb domains, with one inhibitor head close to residue 42 and to the protein active site. To further validate the structural results, we mutated Trp42 to Ala in MNV RdRp and the corresponding residue (i.e., Tyr41 to Ala) in hNV RdRp. Both NF023 and Suramin displayed reduced inhibitory potency versus the mutated hNV RdRp, thus hinting at a conserved inhibitor binding mode in the two polymerases.	+
-		+
-	Structure-Based Inhibition of Norovirus RNA-Dependent RNA Polymerases.,Mastrangelo E, Pezzullo M, Tarantino D, Petazzi R, Germani F, Kramer D, Robel I, Rohayem J, Bolognesi M, Milani M J Mol Biol. 2012 Mar 21. PMID:22446684<ref>PMID:22446684</~~ref>~~	+
-		+
-	~~From MEDLINE®~~/~~PubMed®, a database of the U~~.S. ~~National Library of Medicine.<br>~~	+
-	</~~div>~~	+
-	~~<div class="pdbe-citations 3upf" style="background-color:#fffaf0;"><~~/~~div>~~	+

	==See Also==		==See Also==
	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]		*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Murine norovirus 1]]		[[Category: Murine norovirus 1]]
-	[[Category: Bolognesi, M]]	+	[[Category: Bolognesi M]]
-	[[Category: Mastrangelo, E]]	+	[[Category: Mastrangelo E]]
-	[[Category: Milani, M]]	+	[[Category: Milani M]]
-	~~[[Category: Murine norovirus]]~~	+
-	~~[[Category: Rna-dependent rna polymerase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:55, 20 July 2022

OCA — Wed, 20 Jul 2022 07:55:28 GMT

←Older revision		Revision as of 07:55, 20 July 2022
Line 1:		Line 1:

	==Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023==		==Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023==
-	<StructureSection load='3upf' size='340' side='right' caption='[[3upf]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='3upf' size='340' side='right'caption='[[3upf]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3UPF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UPF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nah\|3nah]], [[3nai\|3nai]], [[3uqs\|3uqs]], [[3ur0\|3ur0]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nah\|3nah]], [[3nai\|3nai]], [[3uqs\|3uqs]], [[3ur0\|3ur0]]</div></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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [~~http~~://pdbe.org/3upf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3upf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3upf 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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [https://pdbe.org/3upf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [https://www.ebi.ac.uk/pdbsum/3upf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3upf ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 19:		Line 19:

	==See Also==		==See Also==
-	*[[RNA polymerase\|RNA polymerase]]	+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Murine norovirus 1]]		[[Category: Murine norovirus 1]]
	[[Category: Bolognesi, M]]		[[Category: Bolognesi, M]]

OCA at 20:33, 11 August 2016

OCA — Thu, 11 Aug 2016 20:33:08 GMT

←Older revision		Revision as of 20:33, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023==		==Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023==
	<StructureSection load='3upf' size='340' side='right' caption='[[3upf]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='3upf' size='340' side='right' caption='[[3upf]], [[Resolution\|resolution]] 2.60Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nah\|3nah]], [[3nai\|3nai]], [[3uqs\|3uqs]], [[3ur0\|3ur0]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nah\|3nah]], [[3nai\|3nai]], [[3uqs\|3uqs]], [[3ur0\|3ur0]]</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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [http://www.ebi.ac.uk/pdbsum/3upf PDBsum]</span></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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [http://pdbe.org/3upf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [http://www.ebi.ac.uk/pdbsum/3upf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3upf ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 15:		Line 16:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3upf" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 10:17, 4 January 2015

OCA — Sun, 04 Jan 2015 10:17:23 GMT

←Older revision		Revision as of 10:17, 4 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UPF FirstGlance]. <br>		<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UPF FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nah\|3nah]], [[3nai\|3nai]], [[3uqs\|3uqs]], [[3ur0\|3ur0]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nah\|3nah]], [[3nai\|3nai]], [[3uqs\|3uqs]], [[3ur0\|3ur0]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [http://www.ebi.ac.uk/pdbsum/3upf PDBsum]</span></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=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [http://www.ebi.ac.uk/pdbsum/3upf PDBsum]</span></td></tr>
-	<table>	+	</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 13:		Line 13:
	Structure-Based Inhibition of Norovirus RNA-Dependent RNA Polymerases.,Mastrangelo E, Pezzullo M, Tarantino D, Petazzi R, Germani F, Kramer D, Robel I, Rohayem J, Bolognesi M, Milani M J Mol Biol. 2012 Mar 21. PMID:22446684<ref>PMID:22446684</ref>		Structure-Based Inhibition of Norovirus RNA-Dependent RNA Polymerases.,Mastrangelo E, Pezzullo M, Tarantino D, Petazzi R, Germani F, Kramer D, Robel I, Rohayem J, Bolognesi M, Milani M J Mol Biol. 2012 Mar 21. PMID:22446684<ref>PMID:22446684</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, a database of the U.S. National Library of Medicine.<br>	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>

Line 23:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Murine norovirus 1]]		[[Category: Murine norovirus 1]]
-	[[Category: Bolognesi, M.]]	+	[[Category: Bolognesi, M]]
-	[[Category: Mastrangelo, E.]]	+	[[Category: Mastrangelo, E]]
-	[[Category: Milani, M.]]	+	[[Category: Milani, M]]
	[[Category: Murine norovirus]]		[[Category: Murine norovirus]]
	[[Category: Rna-dependent rna polymerase]]		[[Category: Rna-dependent rna polymerase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:43, 5 June 2014

OCA — Thu, 05 Jun 2014 05:43:56 GMT

←Older revision		Revision as of 05:43, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~3upf.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023==
		+	<StructureSection load='3upf' size='340' side='right' caption='[[3upf]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3upf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UPF FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BU:8-({3-[({3-[(4,6,8-TRISULFONAPHTHALEN-1-YL)CARBAMOYL]PHENYL}CARBAMOYL)AMINO]BENZOYL}AMINO)NAPHTHALENE-1,3,5-TRISULFONIC+ACID'>0BU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nah\|3nah]], [[3nai\|3nai]], [[3uqs\|3uqs]], [[3ur0\|3ur0]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3upf RCSB], [http://www.ebi.ac.uk/pdbsum/3upf PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Caliciviridae are RNA viruses with a single-stranded, positively oriented polyadenylated genome, responsible for a broad spectrum of diseases such as acute gastroenteritis in humans. Recently, analyses on the structures and functionalities of the RNA-dependent RNA polymerase (RdRp) from several Caliciviruses have been reported. The RdRp is predicted to play a key role in genome replication, as well as in synthesis and amplification of additional subgenomic RNA. Starting from the crystal structures of human Norovirus (hNV) RdRp, we performed an in silico docking search to identify synthetic compounds with predicted high affinity for the enzyme active site. The best-ranked candidates were tested in vitro on murine Norovirus (MNV) and hNV RdRps to assay their inhibition of RNA polymerization. The results of such combined computational and experimental screening approach led to the identification of two high-potency inhibitors: Suramin and NF023, both symmetric divalent molecules hosting two naphthalene-trisulfonic acid heads. We report here the crystal structure of MNV RdRp alone and in the presence of the two identified inhibitors. Both inhibitory molecules occupy the same RdRp site, between the fingers and thumb domains, with one inhibitor head close to residue 42 and to the protein active site. To further validate the structural results, we mutated Trp42 to Ala in MNV RdRp and the corresponding residue (i.e., Tyr41 to Ala) in hNV RdRp. Both NF023 and Suramin displayed reduced inhibitory potency versus the mutated hNV RdRp, thus hinting at a conserved inhibitor binding mode in the two polymerases.

-	<!--	+	Structure-Based Inhibition of Norovirus RNA-Dependent RNA Polymerases.,Mastrangelo E, Pezzullo M, Tarantino D, Petazzi R, Germani F, Kramer D, Robel I, Rohayem J, Bolognesi M, Milani M J Mol Biol. 2012 Mar 21. PMID:22446684<ref>PMID:22446684</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3upf"~~, ~~creates the "Structure Box" on the page.~~	+
-	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded)~~,	+
-	~~or leave the SCENE parameter empty for the default display~~.	+
-	-->	+
-	~~{{STRUCTURE_3upf\| PDB=3upf \| SCENE= }}~~	+

-	~~===Crystal structure~~ of ~~murine norovirus RNA-dependent RNA polymerase bound to NF023===~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	~~<!--~~	+	*[[RNA polymerase\|RNA polymerase]]
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22446684}}, adds the Publication Abstract to the page~~	+	== References ==
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 22446684 is the PubMed ID number.~~	+	<references/>
-	~~-->~~	+	__TOC__
-	~~{{ABSTRACT_PUBMED_22446684}}~~	+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[~~3upf~~]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA].	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022446684<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Murine norovirus 1]]		[[Category: Murine norovirus 1]]
	[[Category: Bolognesi, M.]]		[[Category: Bolognesi, M.]]

OCA at 05:05, 23 May 2012

OCA — Wed, 23 May 2012 05:05:20 GMT

←Older revision		Revision as of 05:05, 23 May 2012
Line 1:		Line 1:
-	[[Image:3upf.~~jpg~~\|left\|200px]]	+	[[Image:3upf.png\|left\|200px]]

	<!--		<!--

OCA at 19:16, 2 May 2012

OCA — Wed, 02 May 2012 19:16:53 GMT

←Older revision		Revision as of 19:16, 2 May 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3upf.jpg\|left\|200px]]

-	The ~~entry 3upf~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3upf", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3upf\| PDB=3upf \| SCENE= }}

-	~~Authors: Milani, M., Mastrangelo, E., Bolognesi, M.~~	+	===Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023===

-	~~Description~~: ~~Crystal~~ structure ~~of murine~~ norovirus ~~RNA~~-dependent ~~RNA~~ polymerase ~~bound to NF023~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22446684}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22446684 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22446684}}
		+
		+	==About this Structure==
		+	[[3upf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPF OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022446684</ref><references group="xtra"/>
		+	[[Category: Murine norovirus 1]]
		+	[[Category: Bolognesi, M.]]
		+	[[Category: Mastrangelo, E.]]
		+	[[Category: Milani, M.]]
		+	[[Category: Murine norovirus]]
		+	[[Category: Rna-dependent rna polymerase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:11, 28 March 2012

OCA — Wed, 28 Mar 2012 07:11:39 GMT

←Older revision		Revision as of 07:11, 28 March 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3upf is ON HOLD	+	The entry 3upf is ON HOLD until Paper Publication

	Authors: Milani, M., Mastrangelo, E., Bolognesi, M.		Authors: Milani, M., Mastrangelo, E., Bolognesi, M.

	Description: Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023		Description: Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023

OCA: Protected "3upf" [edit=sysop:move=sysop]

OCA — Wed, 30 Nov 2011 05:53:33 GMT

Protected "3upf" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:53, 30 November 2011

OCA: New page: '''Unreleased structure''' The entry 3upf is ON HOLD Authors: Milani, M., Mastrangelo, E., Bolognesi, M. Description: Crystal structure of murine norovirus RNA-dependent RNA polymerase...

OCA — Wed, 30 Nov 2011 05:53:32 GMT

New page: '''Unreleased structure''' The entry 3upf is ON HOLD Authors: Milani, M., Mastrangelo, E., Bolognesi, M. Description: Crystal structure of murine norovirus RNA-dependent RNA polymerase...

New page

'''Unreleased structure'''

The entry 3upf is ON HOLD

Authors: Milani, M., Mastrangelo, E., Bolognesi, M.

Description: Crystal structure of murine norovirus RNA-dependent RNA polymerase bound to NF023