2hal - Revision history

OCA at 09:54, 30 August 2023

2023-08-30T09:54:29Z

← Older revision		Revision as of 09:54, 30 August 2023
Line 3:		Line 3:
	<StructureSection load='2hal' size='340' side='right'caption='[[2hal]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='2hal' size='340' side='right'caption='[[2hal]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Hav Hav~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HAL FirstGlance]. <br>		<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatovirus_A Hepatovirus A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HAL FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=BBL:N~~-[~~(BENZYLOXY)CARBONYL~~]~~-L-ALANINE'>BBL</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]] 1.35Å</td></tr>
	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene~~></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2h6m\|2h6m]], [[2h9h\|2h9h]], [[2a4o\|2a4o]], [[2cxv\|2cxv]], [[1hav\|1hav]], [[1qa7\|1qa7]]</div></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 HAV])</td></tr>~~
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [https://pdbe.org/2hal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [https://www.ebi.ac.uk/pdbsum/2hal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hal 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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [https://pdbe.org/2hal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [https://www.ebi.ac.uk/pdbsum/2hal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hal ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/~~POLG_HAVMB POLG_HAVMB]~~] Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome. All these 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 HAVCR1 to provide virion attachment to target cell (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids. The N-terminal domain of VP0, protein VP4, is needed for the assembly of 12 pentamers into the icosahedral structure. Unlike other picornaviruses, HAV VP4 does not seem to be myristoylated and has not been detected in mature virions, supposedly owing to its small size ~~(By similarity)~~. VP1-2A precursor is a component of immature procapsids and corresponds to an extended form of the structural protein VP1. The C-terminal domain of VP1-2A, protein 2A, acts as an assembly signal that allows ~~multimerization~~ of ~~VP1~~-2A ~~and formation~~ of ~~pentamers of VP1-VP2-VP3 trimers~~. It is proteolytically removed from ~~the precursor~~ by a host protease and does not seem to be found in mature particles ~~(By similarity)~~. Protein 2B and 2BC precursor affect 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 to the 3AB and 3ABC precursors ~~(By similarity)~~. The 3AB precursor interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome. Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs ~~(By similarity)~~. The 3ABC precursor is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein ~~(By similarity)~~. Protein 3B is covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. It 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. Also cleaves host proteins such as PCBP2 ~~(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_HAVHM POLG_HAVHM] Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome. All these 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 HAVCR1 to provide virion attachment to target cell (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids. The N-terminal domain of VP0, protein VP4, is needed for the assembly of 12 pentamers into the icosahedral structure. Unlike other picornaviruses, HAV VP4 does not seem to be myristoylated and has not been detected in mature virions, supposedly owing to its small size. VP1-2A precursor is a component of immature procapsids and corresponds to an extended form of the structural protein VP1. The C-terminal domain of VP1-2A, protein 2A, acts as an assembly signal that allows pentamerization of P1-2A, which is the precursor of the structural proteins. 2A is proteolytically removed from particulate VP1-2A by a host protease and does not seem to be found in mature particles. Protein 2B and 2BC precursor affect membrane integrity and cause an increase in membrane permeability. 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 to the 3AB and 3ABC precursors. The 3AB precursor interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome. Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs. The 3ABC precursor is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein. Protein 3B is covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. It acts as a genome-linked replication primer. 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. Also cleaves host proteins such as PCBP2. RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==See Also==		==See Also==
			*[[Proteinase 3D structures\|Proteinase 3D structures]]
	*[[Virus protease 3D structures\|Virus protease 3D structures]]		*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Hav~~]]		[[Category: Hepatovirus A]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Picornain 3C]]~~		[[Category: Bergmann EM]]
	[[Category: Bergmann~~, E M~~]]		[[Category: Cherney MM]]
	[[Category: Cherney~~, M M~~]]		[[Category: James MN]]
	[[Category: James~~, M N~~]]		[[Category: Yin J]]
	[[Category: Yin, J]]
	~~[[Category: 3c protease]]~~
	~~[[Category: Episulfide]]~~
	~~[[Category: Hepatitis a virus]]~~
	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~
	~~[[Category: Inhibitor design]]~~
	~~[[Category: Methylketone]]~~
	~~[[Category: Picornain~~]]

OCA at 07:35, 17 March 2021

2021-03-17T07:35:20Z

← Older revision		Revision as of 07:35, 17 March 2021
Line 1:		Line 1:

	==An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors==		==An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors==
	<StructureSection load='2hal' size='340' side='right' caption='[[2hal]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='2hal' size='340' side='right'caption='[[2hal]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Hav Hav]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2HAL FirstGlance]. <br>		<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hav Hav]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HAL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h6m\|2h6m]], [[2h9h\|2h9h]], [[2a4o\|2a4o]], [[2cxv\|2cxv]], [[1hav\|1hav]], [[1qa7\|1qa7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2h6m\|2h6m]], [[2h9h\|2h9h]], [[2a4o\|2a4o]], [[2cxv\|2cxv]], [[1hav\|1hav]], [[1qa7\|1qa7]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 HAV])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 HAV])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [~~http~~://pdbe.org/2hal PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2hal PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2hal 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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [https://pdbe.org/2hal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [https://www.ebi.ac.uk/pdbsum/2hal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hal ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/POLG_HAVMB POLG_HAVMB]] Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome. All these 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 HAVCR1 to provide virion attachment to target cell (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids. The N-terminal domain of VP0, protein VP4, is needed for the assembly of 12 pentamers into the icosahedral structure. Unlike other picornaviruses, HAV VP4 does not seem to be myristoylated and has not been detected in mature virions, supposedly owing to its small size (By similarity). VP1-2A precursor is a component of immature procapsids and corresponds to an extended form of the structural protein VP1. The C-terminal domain of VP1-2A, protein 2A, acts as an assembly signal that allows multimerization of VP1-2A and formation of pentamers of VP1-VP2-VP3 trimers. It is proteolytically removed from the precursor by a host protease and does not seem to be found in mature particles (By similarity). Protein 2B and 2BC precursor affect 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 to the 3AB and 3ABC precursors (By similarity). The 3AB precursor interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome. Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs (By similarity). The 3ABC precursor is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein (By similarity). Protein 3B is covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. It 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. Also cleaves host proteins such as PCBP2 (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_HAVMB POLG_HAVMB]] Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome. All these 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 HAVCR1 to provide virion attachment to target cell (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids. The N-terminal domain of VP0, protein VP4, is needed for the assembly of 12 pentamers into the icosahedral structure. Unlike other picornaviruses, HAV VP4 does not seem to be myristoylated and has not been detected in mature virions, supposedly owing to its small size (By similarity). VP1-2A precursor is a component of immature procapsids and corresponds to an extended form of the structural protein VP1. The C-terminal domain of VP1-2A, protein 2A, acts as an assembly signal that allows multimerization of VP1-2A and formation of pentamers of VP1-VP2-VP3 trimers. It is proteolytically removed from the precursor by a host protease and does not seem to be found in mature particles (By similarity). Protein 2B and 2BC precursor affect 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 to the 3AB and 3ABC precursors (By similarity). The 3AB precursor interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome. Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs (By similarity). The 3ABC precursor is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein (By similarity). Protein 3B is covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. It 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. Also cleaves host proteins such as PCBP2 (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==See Also==		==See Also==
	*[[3C protease\|3C protease]]		*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Hav]]		[[Category: Hav]]
			[[Category: Large Structures]]
	[[Category: Picornain 3C]]		[[Category: Picornain 3C]]
	[[Category: Bergmann, E M]]		[[Category: Bergmann, E M]]

OCA at 06:22, 27 June 2018

2018-06-27T06:22:09Z

← Older revision		Revision as of 06:22, 27 June 2018
Line 1:		Line 1:

	==An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors==		==An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors==
	<StructureSection load='2hal' size='340' side='right' caption='[[2hal]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='2hal' size='340' side='right' caption='[[2hal]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Hepatitis_a_virus Hepatitis a virus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HAL FirstGlance]. <br>		<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hav Hav]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HAL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h6m\|2h6m]], [[2h9h\|2h9h]], [[2a4o\|2a4o]], [[2cxv\|2cxv]], [[1hav\|1hav]], [[1qa7\|1qa7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h6m\|2h6m]], [[2h9h\|2h9h]], [[2a4o\|2a4o]], [[2cxv\|2cxv]], [[1hav\|1hav]], [[1qa7\|1qa7]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 ~~Hepatitis A virus~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 HAV])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [http://pdbe.org/2hal PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [http://www.ebi.ac.uk/pdbsum/2hal 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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [http://pdbe.org/2hal PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [http://www.ebi.ac.uk/pdbsum/2hal PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hal ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 16:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ha/2hal_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ha/2hal_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Hepatitis a virus~~]]		[[Category: Hav]]
	[[Category: Picornain 3C]]		[[Category: Picornain 3C]]
	[[Category: Bergmann, E M]]		[[Category: Bergmann, E M]]
Line 46:		Line 47:
	[[Category: 3c protease]]		[[Category: 3c protease]]
	[[Category: Episulfide]]		[[Category: Episulfide]]
			[[Category: Hepatitis a virus]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Inhibitor design]]		[[Category: Inhibitor design]]
	[[Category: Methylketone]]		[[Category: Methylketone]]
	[[Category: Picornain]]		[[Category: Picornain]]

OCA at 08:37, 7 February 2016

2016-02-07T08:37:24Z

← Older revision		Revision as of 08:37, 7 February 2016
Line 20:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hal ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 23:42, 9 September 2015

2015-09-09T23:42:03Z

← Older revision		Revision as of 23:42, 9 September 2015
Line 8:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 Hepatitis A virus])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 Hepatitis A virus])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [http://www.ebi.ac.uk/pdbsum/2hal 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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [http://pdbe.org/2hal PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [http://www.ebi.ac.uk/pdbsum/2hal PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 30:		Line 30:
	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 2hal" style="background-color:#fffaf0;"></div>

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

OCA at 13:41, 24 December 2014

2014-12-24T13:41:56Z

← Older revision		Revision as of 13:41, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_a_virus Hepatitis a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HAL FirstGlance]. <br>		<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_a_virus Hepatitis a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HAL FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h6m\|2h6m]], [[2h9h\|2h9h]], [[2a4o\|2a4o]], [[2cxv\|2cxv]], [[1hav\|1hav]], [[1qa7\|1qa7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h6m\|2h6m]], [[2h9h\|2h9h]], [[2a4o\|2a4o]], [[2cxv\|2cxv]], [[1hav\|1hav]], [[1qa7\|1qa7]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 Hepatitis A virus])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 Hepatitis A virus])</td></tr>
	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [http://www.ebi.ac.uk/pdbsum/2hal 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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [http://www.ebi.ac.uk/pdbsum/2hal PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/POLG_HAVMB POLG_HAVMB]] Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome. All these 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 HAVCR1 to provide virion attachment to target cell (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids. The N-terminal domain of VP0, protein VP4, is needed for the assembly of 12 pentamers into the icosahedral structure. Unlike other picornaviruses, HAV VP4 does not seem to be myristoylated and has not been detected in mature virions, supposedly owing to its small size (By similarity). VP1-2A precursor is a component of immature procapsids and corresponds to an extended form of the structural protein VP1. The C-terminal domain of VP1-2A, protein 2A, acts as an assembly signal that allows multimerization of VP1-2A and formation of pentamers of VP1-VP2-VP3 trimers. It is proteolytically removed from the precursor by a host protease and does not seem to be found in mature particles (By similarity). Protein 2B and 2BC precursor affect 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 to the 3AB and 3ABC precursors (By similarity). The 3AB precursor interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome. Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs (By similarity). The 3ABC precursor is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein (By similarity). Protein 3B is covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. It 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. Also cleaves host proteins such as PCBP2 (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 37:		Line 39:
	[[Category: Hepatitis a virus]]		[[Category: Hepatitis a virus]]
	[[Category: Picornain 3C]]		[[Category: Picornain 3C]]
	[[Category: Bergmann, E M.]]		[[Category: Bergmann, E M]]
	[[Category: Cherney, M M.]]		[[Category: Cherney, M M]]
	[[Category: James, M N.]]		[[Category: James, M N]]
	[[Category: Yin, J.]]		[[Category: Yin, J]]
	[[Category: 3c protease]]		[[Category: 3c protease]]
	[[Category: Episulfide]]		[[Category: Episulfide]]
	~~[[Category: Hepatitis a virus]]~~
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Inhibitor design]]		[[Category: Inhibitor design]]
	[[Category: Methylketone]]		[[Category: Methylketone]]
	[[Category: Picornain]]		[[Category: Picornain]]

OCA at 10:30, 30 September 2014

2014-09-30T10:30:01Z

← Older revision		Revision as of 10:30, 30 September 2014
Line 1:		Line 1:
	[[Image:~~2hal~~.~~png~~\|~~left~~\|~~200px~~]]		==An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors==
			<StructureSection load='2hal' size='340' side='right' caption='[[2hal]], [[Resolution\|resolution]] 1.35Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[2hal]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_a_virus Hepatitis a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HAL FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene><br>
			<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GLK:(4S)-4-AMINO-5,5-DIHYDROXYPENTANOIC+ACID'>GLK</scene></td></tr>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h6m\|2h6m]], [[2h9h\|2h9h]], [[2a4o\|2a4o]], [[2cxv\|2cxv]], [[1hav\|1hav]], [[1qa7\|1qa7]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 Hepatitis A virus])</td></tr>
			<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></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=2hal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hal OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hal RCSB], [http://www.ebi.ac.uk/pdbsum/2hal PDBsum]</span></td></tr>
			<table>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ha/2hal_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			We have solved the crystal and molecular structures of hepatitis A viral (HAV) 3C proteinase, a cysteine peptidase having a chymotrypsin-like protein fold, in complex with each of three tetrapeptidyl-based methyl ketone inhibitors to resolutions beyond 1.4 A, the highest resolution to date for a 3C or a 3C-Like (e.g. SARS viral main proteinase) peptidase. The residues of the beta-hairpin motif (residues 138-158), an extension of two beta-strands of the C-terminal beta-barrel of HAV 3C are critical for the interactions between the enzyme and the tetrapeptide portion of these inhibitors that are analogous to the residues at the P4 to P1 positions in the natural substrates of picornaviral 3C proteinases. Unexpectedly, the Sgamma of Cys172 forms two covalent bonds with each inhibitor, yielding an unusual episulfide cation (thiiranium ring) stabilized by a nearby oxyanion. This result suggests a mechanism of inactivation of 3C peptidases by methyl ketone inhibitors that is distinct from that occurring in the structurally related serine proteinases or in the papain-like cysteine peptidases. It also provides insight into the mechanisms underlying both the inactivation of HAV 3C by these inhibitors and on the proteolysis of natural substrates by this viral cysteine peptidase.

	~~{{STRUCTURE_2hal\| PDB=2hal \| SCENE= }}~~		An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors.,Yin J, Cherney MM, Bergmann EM, Zhang J, Huitema C, Pettersson H, Eltis LD, Vederas JC, James MN J Mol Biol. 2006 Aug 25;361(4):673-86. Epub 2006 Jul 7. PMID:16860823<ref>PMID:16860823</ref>

	~~===An episulfide cation (thiiranium ring) trapped in~~ the ~~active site~~ of ~~HAV 3C proteinase inactivated by peptide-based ketone inhibitors===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_16860823}}~~		==See Also==
			*[[3C protease\|3C protease]]
	==~~About this Structure~~==		== References ==
	[[~~2hal~~]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_a_virus Hepatitis a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA].		<references/>
			__TOC__
	==~~Reference~~==		</StructureSection>
	<~~ref group="xtra">PMID:016860823<~~/~~ref~~><~~ref group="xtra">PMID:016288920</ref><ref group="xtra">PMID:010603326</ref><ref group="xtra">PMID:009032381</ref><references group="xtra"~~/>
	[[Category: Hepatitis a virus]]		[[Category: Hepatitis a virus]]
	[[Category: Picornain 3C]]		[[Category: Picornain 3C]]

OCA at 12:25, 23 January 2013

2013-01-23T12:25:46Z

← Older revision		Revision as of 12:25, 23 January 2013
Line 1:		Line 1:
	[[Image:2hal.png\|left\|200px]]		[[Image:2hal.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_2hal", 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_2hal\| PDB=2hal \| SCENE= }}		{{STRUCTURE_2hal\| PDB=2hal \| SCENE= }}

	===An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors===		===An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_16860823}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 16860823 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_16860823}}		{{ABSTRACT_PUBMED_16860823}}

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	==Reference==		==Reference==
	<ref group="xtra">PMID:~~16860823~~</ref><ref group="xtra">PMID:~~16288920~~</ref><ref group="xtra">PMID:~~10603326~~</ref><ref group="xtra">PMID:~~9032381~~</ref><references group="xtra"/>		<ref group="xtra">PMID:016860823</ref><ref group="xtra">PMID:016288920</ref><ref group="xtra">PMID:010603326</ref><ref group="xtra">PMID:009032381</ref><references group="xtra"/>
	[[Category: Hepatitis a virus]]		[[Category: Hepatitis a virus]]
	[[Category: Picornain 3C]]		[[Category: Picornain 3C]]
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	[[Category: Episulfide]]		[[Category: Episulfide]]
	[[Category: Hepatitis a virus]]		[[Category: Hepatitis a virus]]
	[[Category: Hydrolase]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Inhibitor design]]		[[Category: Inhibitor design]]
	[[Category: Methylketone]]		[[Category: Methylketone]]
	[[Category: Picornain]]		[[Category: Picornain]]

OCA: Protected "2hal" [edit=sysop:move=sysop]

2011-03-14T23:27:48Z

Protected "2hal" [edit=sysop:move=sysop]

← Older revision	Revision as of 23:27, 14 March 2011
(No difference)

OCA at 23:27, 14 March 2011

2011-03-14T23:27:46Z

← Older revision		Revision as of 23:27, 14 March 2011
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	~~{{Seed}}~~
	[[Image:2hal.png\|left\|200px]]		[[Image:2hal.png\|left\|200px]]

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	==About this Structure==		==About this Structure==
	~~2HAL~~ is a 2 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Hepatitis_a_virus Hepatitis a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA].		[[2hal]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_a_virus Hepatitis a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAL OCA].

	==Reference==		==Reference==
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	[[Category: Episulfide]]		[[Category: Episulfide]]
	[[Category: Hepatitis a virus]]		[[Category: Hepatitis a virus]]
			[[Category: Hydrolase]]
	[[Category: Inhibitor design]]		[[Category: Inhibitor design]]
	[[Category: Methylketone]]		[[Category: Methylketone]]
	[[Category: Picornain]]		[[Category: Picornain]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 12:37:37 2009''~~