5dfj - Revision history

OCA at 12:24, 6 March 2024

2024-03-06T12:24:16Z

←Older revision		Revision as of 12:24, 6 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5dfj]] is a 4 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=5DFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DFJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[5dfj]] is a 4 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=5DFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DFJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.85Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfj OCA], [https://pdbe.org/5dfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dfj RCSB], [https://www.ebi.ac.uk/pdbsum/5dfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dfj 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=5dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfj OCA], [https://pdbe.org/5dfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dfj RCSB], [https://www.ebi.ac.uk/pdbsum/5dfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dfj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/APEX1_HUMAN APEX1_HUMAN] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.<ref>PMID:1719477</ref> <ref>PMID:12524539</ref> <ref>PMID:8355688</ref> <ref>PMID:8621488</ref> <ref>PMID:8932375</ref> <ref>PMID:9108029</ref> <ref>PMID:9207062</ref> <ref>PMID:9804799</ref> <ref>PMID:9560228</ref> <ref>PMID:10023679</ref> <ref>PMID:11118054</ref> <ref>PMID:11452037</ref> <ref>PMID:11832948</ref> <ref>PMID:11809897</ref> <ref>PMID:16617147</ref> <ref>PMID:18439621</ref> <ref>PMID:18809583</ref> <ref>PMID:18179823</ref> <ref>PMID:18579163</ref> <ref>PMID:19188445</ref> <ref>PMID:19401441</ref> <ref>PMID:19934257</ref> <ref>PMID:20699270</ref> <ref>PMID:21496894</ref> <ref>PMID:21762700</ref>		[https://www.uniprot.org/uniprot/APEX1_HUMAN APEX1_HUMAN] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.<ref>PMID:1719477</ref> <ref>PMID:12524539</ref> <ref>PMID:8355688</ref> <ref>PMID:8621488</ref> <ref>PMID:8932375</ref> <ref>PMID:9108029</ref> <ref>PMID:9207062</ref> <ref>PMID:9804799</ref> <ref>PMID:9560228</ref> <ref>PMID:10023679</ref> <ref>PMID:11118054</ref> <ref>PMID:11452037</ref> <ref>PMID:11832948</ref> <ref>PMID:11809897</ref> <ref>PMID:16617147</ref> <ref>PMID:18439621</ref> <ref>PMID:18809583</ref> <ref>PMID:18179823</ref> <ref>PMID:18579163</ref> <ref>PMID:19188445</ref> <ref>PMID:19401441</ref> <ref>PMID:19934257</ref> <ref>PMID:20699270</ref> <ref>PMID:21496894</ref> <ref>PMID:21762700</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. We report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylated CpG dinucleotides. These structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. These snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.
-
-	Capturing snapshots of APE1 processing DNA damage.,Freudenthal BD, Beard WA, Cuneo MJ, Dyrkheeva NS, Wilson SH Nat Struct Mol Biol. 2015 Nov;22(11):924-31. doi: 10.1038/nsmb.3105. Epub 2015, Oct 12. PMID:26458045<ref>PMID:26458045</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5dfj" style="background-color:#fffaf0;"></div>

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

OCA at 10:33, 21 June 2023

2023-06-21T10:33:19Z

←Older revision		Revision as of 10:33, 21 June 2023
Line 1:		Line 1:

	==Human APE1 E96Q/D210N mismatch substrate complex==		==Human APE1 E96Q/D210N mismatch substrate complex==
-	<StructureSection load='5dfj' size='340' side='right' caption='[[5dfj]], [[Resolution\|resolution]] 1.85Å' scene=''>	+	<StructureSection load='5dfj' size='340' side='right'caption='[[5dfj]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5dfj]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DFJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5DFJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5dfj]] is a 4 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=5DFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DFJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-	~~<tr~~ id~~='NonStdRes'><td class~~="~~sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat~~"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene><~~/td></tr>~~	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfj OCA], [https://pdbe.org/5dfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dfj RCSB], [https://www.ebi.ac.uk/pdbsum/5dfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dfj ProSAT]</span></td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b~~></td>~~<td class="sblockDat">[[5dff\|5dff]]~~, ~~[[5dfh\|5dfh]], [[5dfi\|5dfi]]~~<~~/td></tr>~~	+
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b></td><td class="sblockDat">APEX1~~, ~~APE, APE1, APEX, APX, HAP1, REF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+
-	~~<tr id='activity~~'>~~<td class="sblockLbl"><b>Activity:~~</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] </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=5dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfj OCA], [~~http~~://pdbe.org/5dfj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5dfj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5dfj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5dfj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/APEX1_HUMAN APEX1_HUMAN]] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.<ref>PMID:1719477</ref> <ref>PMID:12524539</ref> <ref>PMID:8355688</ref> <ref>PMID:8621488</ref> <ref>PMID:8932375</ref> <ref>PMID:9108029</ref> <ref>PMID:9207062</ref> <ref>PMID:9804799</ref> <ref>PMID:9560228</ref> <ref>PMID:10023679</ref> <ref>PMID:11118054</ref> <ref>PMID:11452037</ref> <ref>PMID:11832948</ref> <ref>PMID:11809897</ref> <ref>PMID:16617147</ref> <ref>PMID:18439621</ref> <ref>PMID:18809583</ref> <ref>PMID:18179823</ref> <ref>PMID:18579163</ref> <ref>PMID:19188445</ref> <ref>PMID:19401441</ref> <ref>PMID:19934257</ref> <ref>PMID:20699270</ref> <ref>PMID:21496894</ref> <ref>PMID:21762700</ref>	+	[https://www.uniprot.org/uniprot/APEX1_HUMAN APEX1_HUMAN] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.<ref>PMID:1719477</ref> <ref>PMID:12524539</ref> <ref>PMID:8355688</ref> <ref>PMID:8621488</ref> <ref>PMID:8932375</ref> <ref>PMID:9108029</ref> <ref>PMID:9207062</ref> <ref>PMID:9804799</ref> <ref>PMID:9560228</ref> <ref>PMID:10023679</ref> <ref>PMID:11118054</ref> <ref>PMID:11452037</ref> <ref>PMID:11832948</ref> <ref>PMID:11809897</ref> <ref>PMID:16617147</ref> <ref>PMID:18439621</ref> <ref>PMID:18809583</ref> <ref>PMID:18179823</ref> <ref>PMID:18579163</ref> <ref>PMID:19188445</ref> <ref>PMID:19401441</ref> <ref>PMID:19934257</ref> <ref>PMID:20699270</ref> <ref>PMID:21496894</ref> <ref>PMID:21762700</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 5dfj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5dfj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Apurinic/apyrimidinic endonuclease 3D structures\|Apurinic/apyrimidinic endonuclease 3D structures]]
		+	*[[Endonuclease 3D structures\|Endonuclease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Freudenthal, B D~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Wilson, S H~~]]	+	[[Category: Synthetic construct]]
-	[[Category: ~~Hydrolase~~]]	+	[[Category: Freudenthal BD]]
-	[[Category: ~~Lyase-dna complex]]~~	+	[[Category: Wilson SH]]
-	~~[[Category: Lyase/dna~~]]	+

OCA at 14:50, 16 November 2017

2017-11-16T14:50:04Z

←Older revision		Revision as of 14:50, 16 November 2017
Line 1:		Line 1:
		+
	==Human APE1 E96Q/D210N mismatch substrate complex==		==Human APE1 E96Q/D210N mismatch substrate complex==
	<StructureSection load='5dfj' size='340' side='right' caption='[[5dfj]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='5dfj' size='340' side='right' caption='[[5dfj]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5dfj]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DFJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5dfj]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DFJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dff\|5dff]], [[5dfh\|5dfh]], [[5dfi\|5dfi]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dff\|5dff]], [[5dfh\|5dfh]], [[5dfi\|5dfi]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">APEX1, APE, APE1, APEX, APX, HAP1, REF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] </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=5dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfj OCA], [http://pdbe.org/5dfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dfj RCSB], [http://www.ebi.ac.uk/pdbsum/5dfj 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=5dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfj OCA], [http://pdbe.org/5dfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dfj RCSB], [http://www.ebi.ac.uk/pdbsum/5dfj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dfj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Freudenthal, B D]]		[[Category: Freudenthal, B D]]
	[[Category: Wilson, S H]]		[[Category: Wilson, S H]]

OCA at 21:51, 30 November 2015

2015-11-30T21:51:41Z

←Older revision		Revision as of 21:51, 30 November 2015
Line 11:		Line 11:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/APEX1_HUMAN APEX1_HUMAN]] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.<ref>PMID:1719477</ref> <ref>PMID:12524539</ref> <ref>PMID:8355688</ref> <ref>PMID:8621488</ref> <ref>PMID:8932375</ref> <ref>PMID:9108029</ref> <ref>PMID:9207062</ref> <ref>PMID:9804799</ref> <ref>PMID:9560228</ref> <ref>PMID:10023679</ref> <ref>PMID:11118054</ref> <ref>PMID:11452037</ref> <ref>PMID:11832948</ref> <ref>PMID:11809897</ref> <ref>PMID:16617147</ref> <ref>PMID:18439621</ref> <ref>PMID:18809583</ref> <ref>PMID:18179823</ref> <ref>PMID:18579163</ref> <ref>PMID:19188445</ref> <ref>PMID:19401441</ref> <ref>PMID:19934257</ref> <ref>PMID:20699270</ref> <ref>PMID:21496894</ref> <ref>PMID:21762700</ref>		[[http://www.uniprot.org/uniprot/APEX1_HUMAN APEX1_HUMAN]] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.<ref>PMID:1719477</ref> <ref>PMID:12524539</ref> <ref>PMID:8355688</ref> <ref>PMID:8621488</ref> <ref>PMID:8932375</ref> <ref>PMID:9108029</ref> <ref>PMID:9207062</ref> <ref>PMID:9804799</ref> <ref>PMID:9560228</ref> <ref>PMID:10023679</ref> <ref>PMID:11118054</ref> <ref>PMID:11452037</ref> <ref>PMID:11832948</ref> <ref>PMID:11809897</ref> <ref>PMID:16617147</ref> <ref>PMID:18439621</ref> <ref>PMID:18809583</ref> <ref>PMID:18179823</ref> <ref>PMID:18579163</ref> <ref>PMID:19188445</ref> <ref>PMID:19401441</ref> <ref>PMID:19934257</ref> <ref>PMID:20699270</ref> <ref>PMID:21496894</ref> <ref>PMID:21762700</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. We report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylated CpG dinucleotides. These structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. These snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.
		+
		+	Capturing snapshots of APE1 processing DNA damage.,Freudenthal BD, Beard WA, Cuneo MJ, Dyrkheeva NS, Wilson SH Nat Struct Mol Biol. 2015 Nov;22(11):924-31. doi: 10.1038/nsmb.3105. Epub 2015, Oct 12. PMID:26458045<ref>PMID:26458045</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5dfj" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 04:09, 16 October 2015

2015-10-16T04:09:05Z

←Older revision		Revision as of 04:09, 16 October 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Human APE1 E96Q/D210N mismatch substrate complex==
-		+	<StructureSection load='5dfj' size='340' side='right' caption='[[5dfj]], [[Resolution\|resolution]] 1.85Å' scene=''>
-	~~The entry~~ 5dfj is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5dfj]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DFJ FirstGlance]. <br>
-	~~Authors~~: ~~Freudenthal~~, B.D., ~~Wilson~~, S.H.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr>
-	~~Description~~: ~~Human APE1 E96Q~~/~~D210N mismatch substrate~~ complex	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dff\|5dff]], [[5dfh\|5dfh]], [[5dfi\|5dfi]]</td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] </span></td></tr>
-	[[Category: Wilson, S.H]]	+	<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=5dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfj OCA], [http://pdbe.org/5dfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dfj RCSB], [http://www.ebi.ac.uk/pdbsum/5dfj PDBsum]</span></td></tr>
-	[[Category: ~~Freudenthal, B.D~~]]	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/APEX1_HUMAN APEX1_HUMAN]] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.<ref>PMID:1719477</ref> <ref>PMID:12524539</ref> <ref>PMID:8355688</ref> <ref>PMID:8621488</ref> <ref>PMID:8932375</ref> <ref>PMID:9108029</ref> <ref>PMID:9207062</ref> <ref>PMID:9804799</ref> <ref>PMID:9560228</ref> <ref>PMID:10023679</ref> <ref>PMID:11118054</ref> <ref>PMID:11452037</ref> <ref>PMID:11832948</ref> <ref>PMID:11809897</ref> <ref>PMID:16617147</ref> <ref>PMID:18439621</ref> <ref>PMID:18809583</ref> <ref>PMID:18179823</ref> <ref>PMID:18579163</ref> <ref>PMID:19188445</ref> <ref>PMID:19401441</ref> <ref>PMID:19934257</ref> <ref>PMID:20699270</ref> <ref>PMID:21496894</ref> <ref>PMID:21762700</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Freudenthal, B D]]
		+	[[Category: Wilson, S H]]
		+	[[Category: Hydrolase]]
		+	[[Category: Lyase-dna complex]]
		+	[[Category: Lyase/dna]]

OCA at 12:12, 7 October 2015

2015-10-07T12:12:24Z

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

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

	Authors: Freudenthal, B.D., Wilson, S.H.		Authors: Freudenthal, B.D., Wilson, S.H.

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

2015-09-02T11:35:10Z

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

←Older revision

Revision as of 11:35, 2 September 2015

OCA: New page: '''Unreleased structure''' The entry 5dfj is ON HOLD Authors: Freudenthal, B.D., Wilson, S.H. Description: Human APE1 E96Q/D210N mismatch substrate complex [[Category: Unreleased Struc...

2015-09-02T11:35:09Z

New page: '''Unreleased structure''' The entry 5dfj is ON HOLD Authors: Freudenthal, B.D., Wilson, S.H. Description: Human APE1 E96Q/D210N mismatch substrate complex [[Category: Unreleased Struc...

New page

'''Unreleased structure'''

The entry 5dfj is ON HOLD

Authors: Freudenthal, B.D., Wilson, S.H.

Description: Human APE1 E96Q/D210N mismatch substrate complex
[[Category: Unreleased Structures]]
[[Category: Wilson, S.H]]
[[Category: Freudenthal, B.D]]