5dp9 - Revision history

OCA at 21:54, 28 June 2023

2023-06-28T21:54:01Z

←Older revision		Revision as of 21:54, 28 June 2023
Line 3:		Line 3:
	<StructureSection load='5dp9' size='340' side='right'caption='[[5dp9]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='5dp9' size='340' side='right'caption='[[5dp9]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5dp9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DP9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5DP9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5dp9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterovirus_A71 Enterovirus A71]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DP9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5EX:ETHYL+(2Z,4S)-4-[(N-{[(CYCLOBUTYLMETHYL)AMINO](OXO)ACETYL}-L-PHENYLALANYL)AMINO]-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENT-2-ENOATE'>5EX</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]] 1.9Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dp3\|5dp3]], [[5dp4\|5dp4]], [[5dp5\|5dp5]], [[5dp6\|5dp6]], [[5dp7\|5dp7]], [[5dp8\|5dp8]], [[5dpa\|5dpa]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5EX:ETHYL+(2Z,4S)-4-[(N-{[(CYCLOBUTYLMETHYL)AMINO](OXO)ACETYL}-L-PHENYLALANYL)AMINO]-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENT-2-ENOATE'>5EX</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5dp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dp9 OCA], [~~http~~://pdbe.org/5dp9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5dp9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5dp9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5dp9 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=5dp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dp9 OCA], [https://pdbe.org/5dp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dp9 RCSB], [https://www.ebi.ac.uk/pdbsum/5dp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dp9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~A9XG43_9ENTO A9XG43_9ENTO~~]] ~~Protein 2C associates~~ with and induces ~~structural rearrangements~~ of ~~intracellular membranes~~. ~~It displays~~ RNA~~-binding~~, ~~nucleotide~~ binding and ~~NTPase activities~~ (By similarity).[~~SAAS~~:~~SAAS000199_004_016611~~] ~~Protein 3C~~ is a ~~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 co~~-~~operatively~~ to the ~~protease~~ (~~By similarity~~).[~~SAAS~~:~~SAAS000199_004_042266~~] RNA-directed RNA polymerase 3D-~~POL replicates~~ genomic and ~~antigenomic~~ RNA ~~by recognizing replications specific signals~~ (~~By similarity~~).[~~SAAS~~:~~SAAS000199_004_010047~~]	+	[https://www.uniprot.org/uniprot/A9XG43_HE71 A9XG43_HE71] Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity). The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity). Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity). During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions.[ARBA:ARBA00024846] Capsid protein VP0: Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation. Allows the capsid to remain inactive before the maturation step.[RuleBase:RU364118] Capsid protein VP1: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome. Capsid protein VP1 mainly forms the vertices of the capsid. Capsid protein VP1 interacts with host cell receptor to provide virion attachment to target host cells. This attachment induces virion internalization. Tyrosine kinases are probably involved in the entry process. After binding to its receptor, the capsid undergoes conformational changes. Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized. Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm. After genome has been released, the channel shrinks.[RuleBase:RU364118] Capsid protein VP2: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.[RuleBase:RU364118] Capsid protein VP3: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.[RuleBase:RU364118] Capsid protein VP4: Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm.[RuleBase:RU364118] Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity). Allows the capsid to remain inactive before the maturation step.[ARBA:ARBA00025202] Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.[ARBA:ARBA00025306] Lies on the inner surface of the capsid shell (By similarity). After binding to the host receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm.[ARBA:ARBA00024643] Protease 2A: Cysteine protease that cleaves viral polyprotein and specific host proteins.[RuleBase:RU364118] Protease 3C: Major viral protease that mediates proteolytic processing of the polyprotein. Cleaves host EIF5B, contributing to host translation shutoff. Cleaves also host PABPC1, contributing to host translation shutoff.[RuleBase:RU364118] Protein 2B: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication.[RuleBase:RU364118] Protein 2C: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.[RuleBase:RU364118] Protein 3A: Localizes the viral replication complex to the surface of membranous vesicles. It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction. This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface.[RuleBase:RU364118] Protein 3AB: Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity.[RuleBase:RU364118] Protein 3CD: Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome.[RuleBase:RU364118] RNA-directed RNA polymerase: Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated.[RuleBase:RU364118] Viral protein genome-linked: acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU. The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome.[RuleBase:RU364118]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5dp9" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5dp9" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Proteinase 3D structures\|Proteinase 3D structures]]
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Enterovirus A71]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cai, Q]]	+	[[Category: Cai Q]]
-	[[Category: Cai, Y]]	+	[[Category: Cai Y]]
-	[[Category: Li, J]]	+	[[Category: Li J]]
-	[[Category: Li, N]]	+	[[Category: Li N]]
-	[[Category: Li, P]]	+	[[Category: Li P]]
-	[[Category: Lin, T]]	+	[[Category: Lin T]]
-	[[Category: Peng, X]]	+	[[Category: Peng X]]
-	[[Category: Wu, C]]	+	[[Category: Wu C]]
-	[[Category: Zhang, L]]	+	[[Category: Zhang L]]
-	~~[[Category: 3c proteinase]]~~	+
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Foot and mouth disease]]~~	+
-	~~[[Category: Hand]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Peptidomimetic]]~~	+
-	~~[[Category: Rupintrivir~~]]	+

OCA at 08:13, 8 April 2020

2020-04-08T08:13:29Z

←Older revision		Revision as of 08:13, 8 April 2020
Line 1:		Line 1:

	==Crystal Structure of EV71 3C Proteinase in complex with compound 9==		==Crystal Structure of EV71 3C Proteinase in complex with compound 9==
-	<StructureSection load='5dp9' size='340' side='right' caption='[[5dp9]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='5dp9' size='340' side='right'caption='[[5dp9]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5dp9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DP9 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5DP9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5dp9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DP9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DP9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EX:ETHYL+(2Z,4S)-4-[(N-{[(CYCLOBUTYLMETHYL)AMINO](OXO)ACETYL}-L-PHENYLALANYL)AMINO]-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENT-2-ENOATE'>5EX</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5EX:ETHYL+(2Z,4S)-4-[(N-{[(CYCLOBUTYLMETHYL)AMINO](OXO)ACETYL}-L-PHENYLALANYL)AMINO]-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENT-2-ENOATE'>5EX</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dp3\|5dp3]], [[5dp4\|5dp4]], [[5dp5\|5dp5]], [[5dp6\|5dp6]], [[5dp7\|5dp7]], [[5dp8\|5dp8]], [[5dpa\|5dpa]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dp3\|5dp3]], [[5dp4\|5dp4]], [[5dp5\|5dp5]], [[5dp6\|5dp6]], [[5dp7\|5dp7]], [[5dp8\|5dp8]], [[5dpa\|5dpa]]</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=5dp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dp9 OCA], [http://pdbe.org/5dp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dp9 RCSB], [http://www.ebi.ac.uk/pdbsum/5dp9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dp9 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5dp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dp9 OCA], [http://pdbe.org/5dp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dp9 RCSB], [http://www.ebi.ac.uk/pdbsum/5dp9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dp9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Cai, Q]]		[[Category: Cai, Q]]
	[[Category: Cai, Y]]		[[Category: Cai, Y]]

OCA at 09:23, 27 September 2017

2017-09-27T09:23:41Z

←Older revision		Revision as of 09:23, 27 September 2017
Line 6:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EX:ETHYL+(2Z,4S)-4-[(N-{[(CYCLOBUTYLMETHYL)AMINO](OXO)ACETYL}-L-PHENYLALANYL)AMINO]-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENT-2-ENOATE'>5EX</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EX:ETHYL+(2Z,4S)-4-[(N-{[(CYCLOBUTYLMETHYL)AMINO](OXO)ACETYL}-L-PHENYLALANYL)AMINO]-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENT-2-ENOATE'>5EX</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dp3\|5dp3]], [[5dp4\|5dp4]], [[5dp5\|5dp5]], [[5dp6\|5dp6]], [[5dp7\|5dp7]], [[5dp8\|5dp8]], [[5dpa\|5dpa]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dp3\|5dp3]], [[5dp4\|5dp4]], [[5dp5\|5dp5]], [[5dp6\|5dp6]], [[5dp7\|5dp7]], [[5dp8\|5dp8]], [[5dpa\|5dpa]]</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=5dp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dp9 OCA], [http://pdbe.org/5dp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dp9 RCSB], [http://www.ebi.ac.uk/pdbsum/5dp9 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=5dp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dp9 OCA], [http://pdbe.org/5dp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dp9 RCSB], [http://www.ebi.ac.uk/pdbsum/5dp9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dp9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 16:21, 10 May 2016

2016-05-10T16:21:34Z

←Older revision		Revision as of 16:21, 10 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5dp9 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of EV71 3C Proteinase in complex with compound 9==
		+	<StructureSection load='5dp9' size='340' side='right' caption='[[5dp9]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5dp9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DP9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DP9 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EX:ETHYL+(2Z,4S)-4-[(N-{[(CYCLOBUTYLMETHYL)AMINO](OXO)ACETYL}-L-PHENYLALANYL)AMINO]-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENT-2-ENOATE'>5EX</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dp3\|5dp3]], [[5dp4\|5dp4]], [[5dp5\|5dp5]], [[5dp6\|5dp6]], [[5dp7\|5dp7]], [[5dp8\|5dp8]], [[5dpa\|5dpa]]</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=5dp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dp9 OCA], [http://pdbe.org/5dp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dp9 RCSB], [http://www.ebi.ac.uk/pdbsum/5dp9 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A9XG43_9ENTO A9XG43_9ENTO]] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[SAAS:SAAS000199_004_016611] Protein 3C is a 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 co-operatively to the protease (By similarity).[SAAS:SAAS000199_004_042266] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: Enterovirus 71 (EV71) is a causative agent of hand, foot and mouth disease (HFMD), which can spread its infection to central nervous and other systems with severe consequence. A key factor in the replication of EV71 is its 3C proteinase (3C(pro)), a significant drug target. Peptidomimetics were employed as inhibitors of this enzyme for developing antivirals. However, the peptide bonds in these peptidomimetics are a source of low bioavailability due to their susceptibility to protease digestion. To produce non-peptidomimetic inhibitors by replacing these peptide bonds, it would be important to gain better understanding on the contribution of each component to the interaction and potency. METHODS: A series of compounds of different lengths targeting 3C(pro) and having an alpha,beta-unsaturated ester as the warhead were synthesized and their interactions with the enzyme were evaluated by complex structure analyses and potency assays for a better understanding on the relationship between potency and evolution of interaction. RESULTS: The P2 moiety of the compound would need to be oriented to interact in the S2 site in the substrate binding cleft and the P3-P4 moieties were required to generate sufficient potency. A hydrophobic terminal group will benefit the cellular uptake and improve the activity in vivo. CONCLUSIONS AND GENERAL SIGNIFICANCE: The data presented here provide a basis for designing a new generation of non-peptidomimetics to target EV71 3C(pro).

-	~~Authors:~~ Wu, C., Zhang, L., Li, P., Cai, Q., Peng, X., Li, N., ~~Cai~~, Y., Li, J., ~~Lin~~, T.	+	Fragment-wise design of inhibitors to 3C proteinase from enterovirus 71.,Wu C, Zhang L, Li P, Cai Q, Peng X, Yin K, Chen X, Ren H, Zhong S, Weng Y, Guan Y, Chen S, Wu J, Li J, Lin T Biochim Biophys Acta. 2016 Jun;1860(6):1299-307. doi:, 10.1016/j.bbagen.2016.03.017. Epub 2016 Mar 15. PMID:26987809<ref>PMID:26987809</ref>

-	~~Description: Crystal Structure~~ of ~~EV71 3C Proteinase in complex with compound 9~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5dp9" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Cai, Q]]		[[Category: Cai, Q]]
-	[[Category: Lin, T]]
-	[[Category: Li, J]]
-	[[Category: Zhang, L]]
-	[[Category: Wu, C]]
-	[[Category: Peng, X]]
	[[Category: Cai, Y]]		[[Category: Cai, Y]]
		+	[[Category: Li, J]]
	[[Category: Li, N]]		[[Category: Li, N]]
	[[Category: Li, P]]		[[Category: Li, P]]
		+	[[Category: Lin, T]]
		+	[[Category: Peng, X]]
		+	[[Category: Wu, C]]
		+	[[Category: Zhang, L]]
		+	[[Category: 3c proteinase]]
		+	[[Category: Drug design]]
		+	[[Category: Foot and mouth disease]]
		+	[[Category: Hand]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Peptidomimetic]]
		+	[[Category: Rupintrivir]]

OCA at 11:18, 16 December 2015

2015-12-16T11:18:32Z

←Older revision		Revision as of 11:18, 16 December 2015
Line 10:		Line 10:
	[[Category: Lin, T]]		[[Category: Lin, T]]
	[[Category: Li, J]]		[[Category: Li, J]]
-	[[Category: Peng, X]]
-	[[Category: Cai, Y]]
-	[[Category: Li, P]]
	[[Category: Zhang, L]]		[[Category: Zhang, L]]
	[[Category: Wu, C]]		[[Category: Wu, C]]
		+	[[Category: Peng, X]]
		+	[[Category: Cai, Y]]
	[[Category: Li, N]]		[[Category: Li, N]]
		+	[[Category: Li, P]]

OCA at 02:33, 16 October 2015

2015-10-16T02:33:47Z

←Older revision		Revision as of 02:33, 16 October 2015
Line 5:		Line 5:
	Authors: Wu, C., Zhang, L., Li, P., Cai, Q., Peng, X., Li, N., Cai, Y., Li, J., Lin, T.		Authors: Wu, C., Zhang, L., Li, P., Cai, Q., Peng, X., Li, N., Cai, Y., Li, J., Lin, T.

-	Description: Crystal Structure of EV71 3C Proteinase in complex with compound 8	+	Description: Crystal Structure of EV71 3C Proteinase in complex with compound 9
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Cai, Q]]		[[Category: Cai, Q]]

OCA at 12:27, 7 October 2015

2015-10-07T12:27:50Z

←Older revision		Revision as of 12:27, 7 October 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5dp9 is ON HOLD	+	The entry 5dp9 is ON HOLD until Paper Publication

	Authors: Wu, C., Zhang, L., Li, P., Cai, Q., Peng, X., Li, N., Cai, Y., Li, J., Lin, T.		Authors: Wu, C., Zhang, L., Li, P., Cai, Q., Peng, X., Li, N., Cai, Y., Li, J., Lin, T.

OCA: Protected "5dp9" [edit=sysop:move=sysop]

2015-09-30T13:19:25Z

Protected "5dp9" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:19, 30 September 2015

OCA: New page: '''Unreleased structure''' The entry 5dp9 is ON HOLD Authors: Wu, C., Zhang, L., Li, P., Cai, Q., Peng, X., Li, N., Cai, Y., Li, J., Lin, T. Description: Crystal Structure of EV71 3C P...

2015-09-30T13:19:23Z

New page: '''Unreleased structure''' The entry 5dp9 is ON HOLD Authors: Wu, C., Zhang, L., Li, P., Cai, Q., Peng, X., Li, N., Cai, Y., Li, J., Lin, T. Description: Crystal Structure of EV71 3C P...

New page

'''Unreleased structure'''

The entry 5dp9 is ON HOLD

Authors: Wu, C., Zhang, L., Li, P., Cai, Q., Peng, X., Li, N., Cai, Y., Li, J., Lin, T.

Description: Crystal Structure of EV71 3C Proteinase in complex with compound 8
[[Category: Unreleased Structures]]
[[Category: Cai, Q]]
[[Category: Lin, T]]
[[Category: Li, J]]
[[Category: Peng, X]]
[[Category: Cai, Y]]
[[Category: Li, P]]
[[Category: Zhang, L]]
[[Category: Wu, C]]
[[Category: Li, N]]