5h6l - Revision history

OCA at 09:15, 20 March 2024

OCA — Wed, 20 Mar 2024 09:15:15 GMT

←Older revision		Revision as of 09:15, 20 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PRSN_PIERA PRSN_PIERA] ADP-ribosylates double-stranded DNA by targeting the N2 amino group of dG residues; 10-fold less active on tRNA. Induces apoptosis in a range of human cell lines (PubMed:10485873, PubMed:11592983). May play a role in removing unnecessary or harmful cells during pupation (PubMed:15528160) (Probable). May play a role in defense against parasitic wasps; its habitual predator Cotesia glomerata is only susceptible after removal of its eggshell or the surface of the larval caudal vesicle, while other wasps are damaged by this protein (PubMed:23637752) (Probable). The wild-type catalytic domain (residues 1-233) cannot be expressed in E.coli as it is unstable probably due to its toxicity. A catalytic domain fragment (Glu-165 mutated to Gln) binds dsDNA but not ssDNA; the presence of the linker inhibits DNA-binding (PubMed:28765284).<ref>PMID:10485873</ref> <ref>PMID:11592983</ref> <ref>PMID:28765284</ref> <ref>PMID:15528160</ref> <ref>PMID:23637752</ref>		[https://www.uniprot.org/uniprot/PRSN_PIERA PRSN_PIERA] ADP-ribosylates double-stranded DNA by targeting the N2 amino group of dG residues; 10-fold less active on tRNA. Induces apoptosis in a range of human cell lines (PubMed:10485873, PubMed:11592983). May play a role in removing unnecessary or harmful cells during pupation (PubMed:15528160) (Probable). May play a role in defense against parasitic wasps; its habitual predator Cotesia glomerata is only susceptible after removal of its eggshell or the surface of the larval caudal vesicle, while other wasps are damaged by this protein (PubMed:23637752) (Probable). The wild-type catalytic domain (residues 1-233) cannot be expressed in E.coli as it is unstable probably due to its toxicity. A catalytic domain fragment (Glu-165 mutated to Gln) binds dsDNA but not ssDNA; the presence of the linker inhibits DNA-binding (PubMed:28765284).<ref>PMID:10485873</ref> <ref>PMID:11592983</ref> <ref>PMID:28765284</ref> <ref>PMID:15528160</ref> <ref>PMID:23637752</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	ADP-ribosyltransferases transfer the ADP-ribose moiety of betaNAD+ to an acceptor molecule, usually a protein that modulates the function of the acceptor. Pierisin-1 is an ADP-ribosyltransferase from the cabbage butterfly Pieris rapae and is composed of N-terminal catalytic and C-terminal ricin B-like domains. Curiously, it ADP-ribosylates the DNA duplex, resulting in apoptosis of various cancer cells, which has raised interest in pierisin-1 as an anti-cancer agent. However, both the structure and the mechanism of DNA ADP-ribosylation are unclear. Here, we report the crystal structures of the N-terminal catalytic domain of pierisin-1, its complex with betaNAD+, and the catalytic domain with the linker connecting it to the ricin B-like domains. We found that the catalytic domain possesses a defined, positively charged region on the molecular surface but that its overall structure is otherwise similar to those of protein-targeting ADP-ribosyltransferases. Electrophoretic mobility shift assays and site-directed mutagenesis indicated that pierisin-1 binds double-stranded but not single-stranded DNA and that Lys122, Lys123, and Lys124, which are found in a loop, and Arg181 and Arg187, located in a basic cleft near the loop, are required for DNA binding. Furthermore, the structure of the catalytic domain with the linker revealed an autoinhibitory mechanism in which the linker occupies and blocks both the betaNAD+- and DNA-binding sites, suggesting that proteolytic cleavage to remove the linker is necessary for enzyme catalysis. Our study provides a structural basis for the DNA-acceptor specificity of pierisin-1 and reveals that a self-regulatory mechanism is required for its activity.
-
-	Structural basis of autoinhibition and activation of the DNA-targeting ADP-ribosyltransferase pierisin-1.,Oda T, Hirabayashi H, Shikauchi G, Takamura R, Hiraga K, Minami H, Hashimoto H, Yamamoto M, Wakabayashi K, Shimizu T, Sato M J Biol Chem. 2017 Sep 15;292(37):15445-15455. doi: 10.1074/jbc.M117.776641. Epub , 2017 Aug 1. PMID:28765284<ref>PMID:28765284</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5h6l" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:25, 9 August 2023

OCA — Wed, 09 Aug 2023 07:25:09 GMT

←Older revision		Revision as of 07:25, 9 August 2023
Line 3:		Line 3:
	<StructureSection load='5h6l' size='340' side='right'caption='[[5h6l]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='5h6l' size='340' side='right'caption='[[5h6l]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5h6l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H6L OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5H6L FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5h6l]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pieris_rapae Pieris rapae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H6L FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=EDO:1~~,2~~-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.1Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~[[5h6j\|5h6j]]~~, ~~[[5h6k\|5h6k]]~~, ~~[[5h6m\|5h6m]], [[5h6n\|5h6n]]~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=5h6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h6l OCA], [~~http~~://pdbe.org/5h6l PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5h6l RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5h6l PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5h6l 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=5h6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h6l OCA], [https://pdbe.org/5h6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h6l RCSB], [https://www.ebi.ac.uk/pdbsum/5h6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h6l ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PRSN_PIERA PRSN_PIERA] ADP-ribosylates double-stranded DNA by targeting the N2 amino group of dG residues; 10-fold less active on tRNA. Induces apoptosis in a range of human cell lines (PubMed:10485873, PubMed:11592983). May play a role in removing unnecessary or harmful cells during pupation (PubMed:15528160) (Probable). May play a role in defense against parasitic wasps; its habitual predator Cotesia glomerata is only susceptible after removal of its eggshell or the surface of the larval caudal vesicle, while other wasps are damaged by this protein (PubMed:23637752) (Probable). The wild-type catalytic domain (residues 1-233) cannot be expressed in E.coli as it is unstable probably due to its toxicity. A catalytic domain fragment (Glu-165 mutated to Gln) binds dsDNA but not ssDNA; the presence of the linker inhibits DNA-binding (PubMed:28765284).<ref>PMID:10485873</ref> <ref>PMID:11592983</ref> <ref>PMID:28765284</ref> <ref>PMID:15528160</ref> <ref>PMID:23637752</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hashimoto, H]]	+	[[Category: Pieris rapae]]
-	[[Category: Hirabayashi, H]]	+	[[Category: Hashimoto H]]
-	[[Category: Hiraga, K]]	+	[[Category: Hirabayashi H]]
-	[[Category: Minami, H]]	+	[[Category: Hiraga K]]
-	[[Category: Oda, T]]	+	[[Category: Minami H]]
-	[[Category: Sato, M]]	+	[[Category: Oda T]]
-	[[Category: Shikauchi, G]]	+	[[Category: Sato M]]
-	[[Category: Shimizu, T]]	+	[[Category: Shikauchi G]]
-	[[Category: Sugimura, T]]	+	[[Category: Shimizu T]]
-	[[Category: Takamura, R]]	+	[[Category: Sugimura T]]
-	[[Category: Wakabayashi, K]]	+	[[Category: Takamura R]]
-	[[Category: Yamamoto, M]]	+	[[Category: Wakabayashi K]]
-	~~[[Category: Dna-targeting adp-ribosyltransferase]]~~	+	[[Category: Yamamoto M]]
-	~~[[Category: Transferase~~]]	+

OCA at 06:53, 20 May 2020

OCA — Wed, 20 May 2020 06:53:53 GMT

←Older revision		Revision as of 06:53, 20 May 2020
Line 1:		Line 1:

	==DNA targeting ADP-ribosyltransferase Pierisin-1 in complex with beta-NAD+==		==DNA targeting ADP-ribosyltransferase Pierisin-1 in complex with beta-NAD+==
-	<StructureSection load='5h6l' size='340' side='right' caption='[[5h6l]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='5h6l' size='340' side='right'caption='[[5h6l]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5h6l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H6L OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5H6L FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5h6l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H6L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5H6L FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5h6j\|5h6j]], [[5h6k\|5h6k]], [[5h6m\|5h6m]], [[5h6n\|5h6n]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5h6j\|5h6j]], [[5h6k\|5h6k]], [[5h6m\|5h6m]], [[5h6n\|5h6n]]</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=5h6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h6l OCA], [http://pdbe.org/5h6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h6l RCSB], [http://www.ebi.ac.uk/pdbsum/5h6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h6l 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=5h6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h6l OCA], [http://pdbe.org/5h6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h6l RCSB], [http://www.ebi.ac.uk/pdbsum/5h6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h6l ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 21:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Hashimoto, H]]		[[Category: Hashimoto, H]]
	[[Category: Hirabayashi, H]]		[[Category: Hirabayashi, H]]

OCA at 10:01, 27 September 2017

OCA — Wed, 27 Sep 2017 10:01:56 GMT

←Older revision		Revision as of 10:01, 27 September 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5h6l is ~~ON HOLD~~	+	==DNA targeting ADP-ribosyltransferase Pierisin-1 in complex with beta-NAD+==
		+	<StructureSection load='5h6l' size='340' side='right' caption='[[5h6l]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5h6l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H6L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H6L FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5h6j\|5h6j]], [[5h6k\|5h6k]], [[5h6m\|5h6m]], [[5h6n\|5h6n]]</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=5h6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h6l OCA], [http://pdbe.org/5h6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h6l RCSB], [http://www.ebi.ac.uk/pdbsum/5h6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h6l ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	ADP-ribosyltransferases transfer the ADP-ribose moiety of betaNAD+ to an acceptor molecule, usually a protein that modulates the function of the acceptor. Pierisin-1 is an ADP-ribosyltransferase from the cabbage butterfly Pieris rapae and is composed of N-terminal catalytic and C-terminal ricin B-like domains. Curiously, it ADP-ribosylates the DNA duplex, resulting in apoptosis of various cancer cells, which has raised interest in pierisin-1 as an anti-cancer agent. However, both the structure and the mechanism of DNA ADP-ribosylation are unclear. Here, we report the crystal structures of the N-terminal catalytic domain of pierisin-1, its complex with betaNAD+, and the catalytic domain with the linker connecting it to the ricin B-like domains. We found that the catalytic domain possesses a defined, positively charged region on the molecular surface but that its overall structure is otherwise similar to those of protein-targeting ADP-ribosyltransferases. Electrophoretic mobility shift assays and site-directed mutagenesis indicated that pierisin-1 binds double-stranded but not single-stranded DNA and that Lys122, Lys123, and Lys124, which are found in a loop, and Arg181 and Arg187, located in a basic cleft near the loop, are required for DNA binding. Furthermore, the structure of the catalytic domain with the linker revealed an autoinhibitory mechanism in which the linker occupies and blocks both the betaNAD+- and DNA-binding sites, suggesting that proteolytic cleavage to remove the linker is necessary for enzyme catalysis. Our study provides a structural basis for the DNA-acceptor specificity of pierisin-1 and reveals that a self-regulatory mechanism is required for its activity.

-	~~Authors~~:	+	Structural basis of autoinhibition and activation of the DNA-targeting ADP-ribosyltransferase pierisin-1.,Oda T, Hirabayashi H, Shikauchi G, Takamura R, Hiraga K, Minami H, Hashimoto H, Yamamoto M, Wakabayashi K, Shimizu T, Sato M J Biol Chem. 2017 Sep 15;292(37):15445-15455. doi: 10.1074/jbc.M117.776641. Epub , 2017 Aug 1. PMID:28765284<ref>PMID:28765284</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5h6l" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Hashimoto, H]]
		+	[[Category: Hirabayashi, H]]
		+	[[Category: Hiraga, K]]
		+	[[Category: Minami, H]]
		+	[[Category: Oda, T]]
		+	[[Category: Sato, M]]
		+	[[Category: Shikauchi, G]]
		+	[[Category: Shimizu, T]]
		+	[[Category: Sugimura, T]]
		+	[[Category: Takamura, R]]
		+	[[Category: Wakabayashi, K]]
		+	[[Category: Yamamoto, M]]
		+	[[Category: Dna-targeting adp-ribosyltransferase]]
		+	[[Category: Transferase]]

OCA: Protected "5h6l" [edit=sysop:move=sysop]

OCA — Fri, 09 Dec 2016 13:48:19 GMT

Protected "5h6l" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:48, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5h6l is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Fri, 09 Dec 2016 13:48:18 GMT

New page: '''Unreleased structure''' The entry 5h6l is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5h6l is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]