4qhd - Revision history

OCA at 12:46, 1 March 2024

OCA — Fri, 01 Mar 2024 12:46:29 GMT

←Older revision		Revision as of 12:46, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qhd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QHD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qhd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QHD 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></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]] 1.65Å</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></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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [https://pdbe.org/4qhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [https://www.ebi.ac.uk/pdbsum/4qhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qhd 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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [https://pdbe.org/4qhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [https://www.ebi.ac.uk/pdbsum/4qhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qhd 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 ==
-	Apurinic/apyrimidinic endonuclease I (APE1) is an essential base excision repair enzyme that catalyzes a Mg(2+)-dependent reaction in which the phosphodiester backbone is cleaved 5' of an abasic site in duplex DNA. This reaction has been proposed to involve either one or two metal ions bound to the active site. In the present study, we report crystal structures of Mg(2+), Mn(2+), and apo-APE1 determined at 1.4, 2.2, and 1.65 A, respectively, representing two of the highest resolution structures yet reported for APE1. In our structures, a single well-ordered Mn(2+) ion was observed coordinated by D70 and E96; the Mg(2+) site exhibited disorder modeled as two closely positioned sites coordinated by D70 and E96 or E96 alone. Direct metal binding analysis of wild-type, D70A, and E96A APE1, as assessed by differential scanning fluorimetry, indicated a role for D70 and E96 in binding of Mg(2+) or Mn(2+) to APE1. Consistent with the disorder exhibited by Mg(2+) bound to the active site, two different conformations of E96 were observed coordinated to Mg(2+). A third conformation for E96 in the apo structure is similar to that observed in the APE1-DNA-Mg(2+) complex structure. Thus, binding of Mg(2+) in three different positions within the active site of APE1 in these crystal structures corresponds directly with three different conformations of E96. Taken together, our results are consistent with the initial capture of metal by D70 and E96 and repositioning of Mg(2+) facilitated by the structural plasticity of E96 in the active site.
-
-	High-resolution crystal structures reveal plasticity in the metal binding site of apurinic/apyrimidinic endonuclease I.,He H, Chen Q, Georgiadis MM Biochemistry. 2014 Oct 21;53(41):6520-9. doi: 10.1021/bi500676p. Epub 2014 Oct 8. PMID:25251148<ref>PMID:25251148</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4qhd" style="background-color:#fffaf0;"></div>

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

OCA at 11:29, 15 February 2023

OCA — Wed, 15 Feb 2023 11:29:55 GMT

←Older revision		Revision as of 11:29, 15 February 2023
Line 3:		Line 3:
	<StructureSection load='4qhd' size='340' side='right'caption='[[4qhd]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='4qhd' size='340' side='right'caption='[[4qhd]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qhd]] is a 1 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=4QHD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QHD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qhd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QHD 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>~~</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></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qh9\|4qh9]], [[4qhe\|4qhe]]</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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [https://pdbe.org/4qhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [https://www.ebi.ac.uk/pdbsum/4qhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qhd ProSAT]</span></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='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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [~~http~~://pdbe.org/4qhd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qhd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qhd 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 27:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen, Q]]	+	[[Category: Chen Q]]
-	[[Category: Georgiadis~~, M M~~]]	+	[[Category: Georgiadis MM]]
-	[[Category: He, H]]	+	[[Category: He H]]
-	~~[[Category: Beta sandwich]]~~	+
-	~~[[Category: Dna-binding]]~~	+
-	~~[[Category: Endonuclease]]~~	+
-	~~[[Category: Lyase]]~~	+
-	~~[[Category: Nucleus~~]]	+

OCA at 09:05, 24 April 2019

OCA — Wed, 24 Apr 2019 09:05:59 GMT

←Older revision		Revision as of 09:05, 24 April 2019
Line 1:		Line 1:

	==Crystal structure of apo human APE1==		==Crystal structure of apo human APE1==
-	<StructureSection load='4qhd' size='340' side='right' caption='[[4qhd]], [[Resolution\|resolution]] 1.65Å' scene=''>	+	<StructureSection load='4qhd' size='340' side='right'caption='[[4qhd]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qhd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QHD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QHD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qhd]] is a 1 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=4QHD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QHD 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></td></tr>		</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></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qh9\|4qh9]], [[4qhe\|4qhe]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qh9\|4qh9]], [[4qhe\|4qhe]]</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='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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [http://pdbe.org/4qhd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [http://www.ebi.ac.uk/pdbsum/4qhd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qhd ProSAT]</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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [http://pdbe.org/4qhd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [http://www.ebi.ac.uk/pdbsum/4qhd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qhd ProSAT]</span></td></tr>
	</table>		</table>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4qhd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4qhd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Apurinic/apyrimidinic endonuclease 3D structures\|Apurinic/apyrimidinic endonuclease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Chen, Q]]		[[Category: Chen, Q]]
	[[Category: Georgiadis, M M]]		[[Category: Georgiadis, M M]]

OCA at 11:22, 4 August 2016

OCA — Thu, 04 Aug 2016 11:22:44 GMT

←Older revision		Revision as of 11:22, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of apo human APE1==		==Crystal structure of apo human APE1==
	<StructureSection load='4qhd' size='340' side='right' caption='[[4qhd]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='4qhd' size='340' side='right' caption='[[4qhd]], [[Resolution\|resolution]] 1.65Å' scene=''>
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	</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></td></tr>		</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></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qh9\|4qh9]], [[4qhe\|4qhe]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qh9\|4qh9]], [[4qhe\|4qhe]]</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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [http://www.ebi.ac.uk/pdbsum/4qhd 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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [http://pdbe.org/4qhd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [http://www.ebi.ac.uk/pdbsum/4qhd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qhd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4qhd" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:48, 25 December 2014

OCA — Thu, 25 Dec 2014 08:48:29 GMT

←Older revision		Revision as of 08:48, 25 December 2014
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	<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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [http://www.ebi.ac.uk/pdbsum/4qhd 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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [http://www.ebi.ac.uk/pdbsum/4qhd PDBsum]</span></td></tr>
	</table>		</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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 06:56, 12 November 2014

OCA — Wed, 12 Nov 2014 06:56:16 GMT

←Older revision		Revision as of 06:56, 12 November 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of apo human APE1==
		+	<StructureSection load='4qhd' size='340' side='right' caption='[[4qhd]], [[Resolution\|resolution]] 1.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4qhd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QHD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QHD 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></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qh9\|4qh9]], [[4qhe\|4qhe]]</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=4qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qhd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qhd RCSB], [http://www.ebi.ac.uk/pdbsum/4qhd PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Apurinic/apyrimidinic endonuclease I (APE1) is an essential base excision repair enzyme that catalyzes a Mg(2+)-dependent reaction in which the phosphodiester backbone is cleaved 5' of an abasic site in duplex DNA. This reaction has been proposed to involve either one or two metal ions bound to the active site. In the present study, we report crystal structures of Mg(2+), Mn(2+), and apo-APE1 determined at 1.4, 2.2, and 1.65 A, respectively, representing two of the highest resolution structures yet reported for APE1. In our structures, a single well-ordered Mn(2+) ion was observed coordinated by D70 and E96; the Mg(2+) site exhibited disorder modeled as two closely positioned sites coordinated by D70 and E96 or E96 alone. Direct metal binding analysis of wild-type, D70A, and E96A APE1, as assessed by differential scanning fluorimetry, indicated a role for D70 and E96 in binding of Mg(2+) or Mn(2+) to APE1. Consistent with the disorder exhibited by Mg(2+) bound to the active site, two different conformations of E96 were observed coordinated to Mg(2+). A third conformation for E96 in the apo structure is similar to that observed in the APE1-DNA-Mg(2+) complex structure. Thus, binding of Mg(2+) in three different positions within the active site of APE1 in these crystal structures corresponds directly with three different conformations of E96. Taken together, our results are consistent with the initial capture of metal by D70 and E96 and repositioning of Mg(2+) facilitated by the structural plasticity of E96 in the active site.

-	~~The entry 4qhd is ON HOLD~~	+	High-resolution crystal structures reveal plasticity in the metal binding site of apurinic/apyrimidinic endonuclease I.,He H, Chen Q, Georgiadis MM Biochemistry. 2014 Oct 21;53(41):6520-9. doi: 10.1021/bi500676p. Epub 2014 Oct 8. PMID:25251148<ref>PMID:25251148</ref>

-	~~Authors: He~~, H., Chen, Q., Georgiadis, M.M.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of apo human APE1~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Chen, Q]]
		+	[[Category: Georgiadis, M M]]
		+	[[Category: He, H]]
		+	[[Category: Beta sandwich]]
		+	[[Category: Dna-binding]]
		+	[[Category: Endonuclease]]
		+	[[Category: Lyase]]
		+	[[Category: Nucleus]]

OCA: Protected "4qhd" [edit=sysop:move=sysop]

OCA — Wed, 04 Jun 2014 04:58:54 GMT

Protected "4qhd" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:58, 4 June 2014

OCA: New page: '''Unreleased structure''' The entry 4qhd is ON HOLD Authors: He, H., Chen, Q., Georgiadis, M.M. Description: Crystal structure of apo human APE1

OCA — Wed, 04 Jun 2014 04:58:54 GMT

New page: '''Unreleased structure''' The entry 4qhd is ON HOLD Authors: He, H., Chen, Q., Georgiadis, M.M. Description: Crystal structure of apo human APE1

New page

'''Unreleased structure'''

The entry 4qhd is ON HOLD

Authors: He, H., Chen, Q., Georgiadis, M.M.

Description: Crystal structure of apo human APE1