4wyl - Revision history

OCA at 11:28, 9 May 2024

OCA — Thu, 09 May 2024 11:28:34 GMT

←Older revision		Revision as of 11:28, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4wyl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Foot-and-mouth_disease_virus_(strain_C1-Santa_Pau) Foot-and-mouth disease virus (strain C1-Santa Pau)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WYL FirstGlance]. <br>		<table><tr><td colspan='2'>[[4wyl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Foot-and-mouth_disease_virus_(strain_C1-Santa_Pau) Foot-and-mouth disease virus (strain C1-Santa Pau)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WYL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=4wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wyl OCA], [https://pdbe.org/4wyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wyl RCSB], [https://www.ebi.ac.uk/pdbsum/4wyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wyl 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=4wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wyl OCA], [https://pdbe.org/4wyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wyl RCSB], [https://www.ebi.ac.uk/pdbsum/4wyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wyl ProSAT]</span></td></tr>
	</table>		</table>

OCA at 21:03, 12 April 2023

OCA — Wed, 12 Apr 2023 21:03:44 GMT

←Older revision		Revision as of 21:03, 12 April 2023
Line 3:		Line 3:
	<StructureSection load='4wyl' size='340' side='right'caption='[[4wyl]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4wyl' size='340' side='right'caption='[[4wyl]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4wyl]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Fmdv Fmdv~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4WYL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4wyl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Foot-and-mouth_disease_virus_(strain_C1-Santa_Pau) Foot-and-mouth disease virus (strain C1-Santa Pau)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WYL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1wne\|1wne]], [[1u09\|1u09]]</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=4wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wyl OCA], [https://pdbe.org/4wyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wyl RCSB], [https://www.ebi.ac.uk/pdbsum/4wyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wyl ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=4wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wyl OCA], [~~http~~://pdbe.org/4wyl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4wyl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4wyl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4wyl ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/POLG_FMDVS POLG_FMDVS]] The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It cleaves the host translation initiation factors EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription (By similarity). Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with host heparan sulfate and various integrins (alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta6, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids (By similarity). Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity). Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer (By similarity). Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).	+	[https://www.uniprot.org/uniprot/POLG_FMDVS POLG_FMDVS] The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It cleaves the host translation initiation factors EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription (By similarity). Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with host heparan sulfate and various integrins (alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta6, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids (By similarity). Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity). Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer (By similarity). Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==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: Fmdv]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: RNA-directed RNA polymerase]]~~	+	[[Category: Domingo E]]
-	[[Category: Domingo, E]]	+	[[Category: Ferrer-Orta C]]
-	[[Category: Ferrer-Orta, C]]	+	[[Category: Verdaguer N]]
-	~~[[Category: Higuera, I de la~~]]	+	[[Category: De la Higuera I]]
-	[[Category: Verdaguer, N]]	+
-	[[Category: ~~Closed-right hand rna dependent rna polymerase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:04, 23 May 2019

OCA — Thu, 23 May 2019 09:04:55 GMT

←Older revision		Revision as of 09:04, 23 May 2019
Line 1:		Line 1:

	==Mutant K18E of 3D polymerase from Foot-and-Moth Disease Virus==		==Mutant K18E of 3D polymerase from Foot-and-Moth Disease Virus==
-	<StructureSection load='4wyl' size='340' side='right' caption='[[4wyl]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='4wyl' size='340' side='right'caption='[[4wyl]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4wyl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WYL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4wyl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Fmdv Fmdv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WYL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1wne\|1wne]], [[1u09\|1u09]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1wne\|1wne]], [[1u09\|1u09]]</td></tr>
Line 27:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Fmdv]]
		+	[[Category: Large Structures]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Domingo, E]]		[[Category: Domingo, E]]

OCA at 17:05, 22 March 2017

OCA — Wed, 22 Mar 2017 17:05:55 GMT

←Older revision		Revision as of 17:05, 22 March 2017
Line 1:		Line 1:
		+
	==Mutant K18E of 3D polymerase from Foot-and-Moth Disease Virus==		==Mutant K18E of 3D polymerase from Foot-and-Moth Disease Virus==
	<StructureSection load='4wyl' size='340' side='right' caption='[[4wyl]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4wyl' size='340' side='right' caption='[[4wyl]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1wne\|1wne]], [[1u09\|1u09]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1wne\|1wne]], [[1u09\|1u09]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=4wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wyl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wyl RCSB], [http://www.ebi.ac.uk/pdbsum/4wyl 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=4wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wyl OCA], [http://pdbe.org/4wyl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wyl RCSB], [http://www.ebi.ac.uk/pdbsum/4wyl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wyl ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4wyl" style="background-color:#fffaf0;"></div>

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

OCA at 08:44, 17 June 2015

OCA — Wed, 17 Jun 2015 08:44:54 GMT

←Older revision		Revision as of 08:44, 17 June 2015
Line 18:		Line 18:
	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>
		+
		+	==See Also==
		+	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:25, 13 May 2015

OCA — Wed, 13 May 2015 06:25:03 GMT

←Older revision		Revision as of 06:25, 13 May 2015
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/POLG_FMDVS POLG_FMDVS]] The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It cleaves the host translation initiation factors EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription (By similarity). Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with host heparan sulfate and various integrins (alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta6, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids (By similarity). Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity). Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer (By similarity). Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).		[[http://www.uniprot.org/uniprot/POLG_FMDVS POLG_FMDVS]] The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It cleaves the host translation initiation factors EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription (By similarity). Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with host heparan sulfate and various integrins (alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta6, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids (By similarity). Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity). Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer (By similarity). Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The N-terminal region of the FMDV 3D polymerase contains the sequence MRKTKLAPT (residues 16 to 24) that acts as a nuclear localization signal. A previous study showed that substitutions K18E and K20E diminished the transport to the nucleus of 3D and 3CD, and severely impaired virus infectivity. These residues have also been implicated in template binding as seen in the crystal structures of different 3D-RNA elongation complexes. Here we report the biochemical and structural characterization of different mutant polymerases harboring substitutions at residues 18 and 20, in particular K18E, K18A, K20E, K20A and the double mutant KAKA. All mutant enzymes exhibit low RNA binding activity, low processivity and alterations in nucleotide recognition, including increased incorporation of ribavirin monophosphate (RMP) relative to the incorporation of cognate nucleotides, as compared with the wild type enzyme. The structural analysis shows an unprecedented flexibility of the 3D mutant polymerases, including both, global rearrangements of the closed hand architecture and local conformational changes at loop beta9-alpha11 (within the polymerase motif B) and at the template-binding channel. Specifically, in 3D bound to RNA both K18E and K20E induced the opening of new pockets in the template channel where the downstream templating nucleotide at position +2 binds. The comparisons of free and RNA bound enzymes suggest that the structural rearrangements may occur in a concerted mode to regulate both RNA replication, processivity and fidelity. Thus, the N-terminal region of FMDV 3D that acts as a nuclear localization signal and in template binding, is also involved in nucleotide recognition, and can affect the incorporation of nucleotide analogues. IMPORTANCE: The study documents multifunctionality of a nuclear localization signal (NLS) located at the N-terminal region of the foot-and-mouth disease viral polymerase (3D). Amino acid substitutions at this polymerase region can impair the transport of 3D to the nucleus, reduce 3D binding to RNA, and alter the relative incorporation of standard nucleoside-monophosphate versus ribavirin-monophosphate. Structural data reveal that the conformational changes in this region, forming part of the template channel entry, would be involved in nucleotide discrimination. The results have implications for the understanding of viral polymerase function, and for lethal mutagenesis mechanisms.
		+
		+	Multifunctionality of a picornavirus polymerase domain: nuclear localization signal and nucleotide recognition.,Ferrer-Orta C, de la Higuera I, Caridi F, Sanchez-Aparicio MT, Moreno E, Perales C, Singh K, Sarafianos SG, Sobrino F, Domingo E, Verdaguer N J Virol. 2015 Apr 22. pii: JVI.03283-14. PMID:25903341<ref>PMID:25903341</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 13:01, 6 May 2015

OCA — Wed, 06 May 2015 13:01:30 GMT

←Older revision		Revision as of 13:01, 6 May 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Mutant K18E of 3D polymerase from Foot-and-Moth Disease Virus==
-		+	<StructureSection load='4wyl' size='340' side='right' caption='[[4wyl]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~The entry~~ 4wyl is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4wyl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WYL FirstGlance]. <br>
-	~~Authors~~: ~~Ferrer~~-~~Orta~~, C., ~~Verdaguer~~, N., ~~de la Higuera~~, I., ~~Domingo~~, E.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1wne\|1wne]], [[1u09\|1u09]]</td></tr>
-	~~Description~~: ~~Mutant K18E~~ of ~~3D polymerase from Foot~~-and-~~Moth Disease Virus~~	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	<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=4wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wyl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wyl RCSB], [http://www.ebi.ac.uk/pdbsum/4wyl PDBsum]</span></td></tr>
-	[[Category: ~~De La Higuera, I~~]]	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLG_FMDVS POLG_FMDVS]] The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It cleaves the host translation initiation factors EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription (By similarity). Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with host heparan sulfate and various integrins (alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta6, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids (By similarity). Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity). Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer (By similarity). Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
		+	__TOC__
		+	</StructureSection>
		+	[[Category: RNA-directed RNA polymerase]]
	[[Category: Domingo, E]]		[[Category: Domingo, E]]
-	[[Category: Verdaguer, N]]
	[[Category: Ferrer-Orta, C]]		[[Category: Ferrer-Orta, C]]
		+	[[Category: Higuera, I de la]]
		+	[[Category: Verdaguer, N]]
		+	[[Category: Closed-right hand rna dependent rna polymerase]]
		+	[[Category: Transferase]]

OCA at 20:12, 24 December 2014

OCA — Wed, 24 Dec 2014 20:12:46 GMT

←Older revision		Revision as of 20:12, 24 December 2014
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	Description: Mutant K18E of 3D polymerase from Foot-and-Moth Disease Virus		Description: Mutant K18E of 3D polymerase from Foot-and-Moth Disease Virus
		+	[[Category: Unreleased Structures]]
		+	[[Category: De La Higuera, I]]
		+	[[Category: Domingo, E]]
		+	[[Category: Verdaguer, N]]
		+	[[Category: Ferrer-Orta, C]]

OCA: Protected "4wyl" [edit=sysop:move=sysop]

OCA — Wed, 26 Nov 2014 07:13:06 GMT

Protected "4wyl" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:13, 26 November 2014

OCA: New page: '''Unreleased structure''' The entry 4wyl is ON HOLD until Paper Publication Authors: Ferrer-Orta, C., Verdaguer, N., de la Higuera, I., Domingo, E. Description: Mutant K18E of 3D poly...

OCA — Wed, 26 Nov 2014 07:13:05 GMT

New page: '''Unreleased structure''' The entry 4wyl is ON HOLD until Paper Publication Authors: Ferrer-Orta, C., Verdaguer, N., de la Higuera, I., Domingo, E. Description: Mutant K18E of 3D poly...

New page

'''Unreleased structure'''

The entry 4wyl is ON HOLD until Paper Publication

Authors: Ferrer-Orta, C., Verdaguer, N., de la Higuera, I., Domingo, E.

Description: Mutant K18E of 3D polymerase from Foot-and-Moth Disease Virus