OCA at 15:29, 18 October 2023

2023-10-18T15:29:54Z

←Older revision		Revision as of 15:29, 18 October 2023
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-	====	+	==PCNA bound to truncated peptide mimetic==
-	<StructureSection load='7kq1' size='340' side='right'caption='[[7kq1]]' scene=''>	+	<StructureSection load='7kq1' size='340' side='right'caption='[[7kq1]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kq1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KQ1 FirstGlance]. <br>
-	</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=7kq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kq1 OCA], [https://pdbe.org/7kq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7kq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kq1 ProSAT]</span></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]] 3.3Å</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=7kq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kq1 OCA], [https://pdbe.org/7kq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7kq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kq1 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PCNA_HUMAN PCNA_HUMAN] Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.<ref>PMID:19443450</ref> <ref>PMID:18719106</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The human sliding clamp, Proliferating Cell Nuclear Antigen (hPCNA), interacts with over 200 proteins through a conserved binding motif, the PIP-box, to orchestrate DNA replication and repair. It is not clear how changes to the features of a PIP-box modulate protein binding and thus how they fine-tune downstream processes. Here, we present a systematic study of each position within the PIP-box to reveal how hPCNA-interacting peptides bind with drastically varied affinities. We synthesized a series of 27 peptides derived from the native protein p21 with small PIP-box modifications and another series of 19 peptides containing PIP-box binding motifs from other proteins. The hPCNA-binding affinity of all peptides, characterized as K(D) values determined by surface plasmon resonance, spanned a 4000-fold range, from 1.83 nM to 7.59 muM. The hPCNA-bound peptide structures determined by X-ray crystallography and modeled computationally revealed intermolecular and intramolecular interaction networks that correlate with high hPCNA affinity. These data informed rational design of three new PIP-box sequences, testing of which revealed the highest affinity hPCNA-binding partner to date, with a K(D) value of 1.12 nM, from a peptide with PIP-box QTRITEYF. This work showcases the sequence-specific nuances within the PIP-box that are responsible for high-affinity hPCNA binding, which underpins our understanding of how nature tunes hPCNA affinity to regulate DNA replication and repair processes. In addition, these insights will be useful to future design of hPCNA inhibitors.
		+
		+	Unlocking the PIP-box: A peptide library reveals interactions that drive high-affinity binding to human PCNA.,Horsfall AJ, Vandborg BA, Kowalczyk W, Chav T, Scanlon DB, Abell AD, Bruning JB J Biol Chem. 2021 Jan-Jun;296:100773. doi: 10.1016/j.jbc.2021.100773. Epub 2021 , May 11. PMID:33984330<ref>PMID:33984330</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kq1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Proliferating cell nuclear antigen 3D structures\|Proliferating cell nuclear antigen 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Synthetic construct]]
		+	[[Category: Bruning JB]]
		+	[[Category: Vandborg BA]]

OCA at 10:10, 19 May 2021

2021-05-19T10:10:01Z

←Older revision		Revision as of 10:10, 19 May 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7kq1 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7kq1' size='340' side='right'caption='[[7kq1]]' scene=''>
-	~~Authors~~: ~~Vandborg, B~~.A.~~, Bruning, J~~.B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~PCNA bound to truncated peptide mimetic~~	+	</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=7kq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kq1 OCA], [https://pdbe.org/7kq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7kq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kq1 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Bruning~~, J.B]]	+	__TOC__
-	[[Category: ~~Vandborg, B.A~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 11:11, 16 December 2020

2020-12-16T11:11:56Z

←Older revision		Revision as of 11:11, 16 December 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7kq1 is ON HOLD	+	The entry 7kq1 is ON HOLD until Paper Publication

	Authors: Vandborg, B.A., Bruning, J.B.		Authors: Vandborg, B.A., Bruning, J.B.

OCA: Protected "7kq1" [edit=sysop:move=sysop]

2020-11-18T08:13:03Z

Protected "7kq1" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:13, 18 November 2020

OCA: New page: '''Unreleased structure''' The entry 7kq1 is ON HOLD Authors: Vandborg, B.A., Bruning, J.B. Description: PCNA bound to truncated peptide mimetic Category: Unreleased Structures [[C...

2020-11-18T08:13:02Z

New page: '''Unreleased structure''' The entry 7kq1 is ON HOLD Authors: Vandborg, B.A., Bruning, J.B. Description: PCNA bound to truncated peptide mimetic Category: Unreleased Structures [[C...

New page

'''Unreleased structure'''

The entry 7kq1 is ON HOLD

Authors: Vandborg, B.A., Bruning, J.B.

Description: PCNA bound to truncated peptide mimetic
[[Category: Unreleased Structures]]
[[Category: Bruning, J.B]]
[[Category: Vandborg, B.A]]

7kq1 - Revision history

OCA at 15:29, 18 October 2023

OCA at 10:10, 19 May 2021

OCA at 11:11, 16 December 2020

OCA: Protected "7kq1" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7kq1 is ON HOLD Authors: Vandborg, B.A., Bruning, J.B. Description: PCNA bound to truncated peptide mimetic Category: Unreleased Structures [[C...