4q5v - Revision history

OCA at 12:44, 1 March 2024

2024-03-01T12:44:23Z

←Older revision		Revision as of 12:44, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4q5v]] is a 6 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=4Q5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q5V FirstGlance]. <br>		<table><tr><td colspan='2'>[[4q5v]] is a 6 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=4Q5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q5V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</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]] 2.52Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [https://pdbe.org/4q5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [https://www.ebi.ac.uk/pdbsum/4q5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q5v 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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [https://pdbe.org/4q5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [https://www.ebi.ac.uk/pdbsum/4q5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q5v ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/DPOLA_HUMAN DPOLA_HUMAN] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.<ref>PMID:9518481</ref>		[https://www.uniprot.org/uniprot/DPOLA_HUMAN DPOLA_HUMAN] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.<ref>PMID:9518481</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Natural tetracyclic diterpenoid aphidicolin is a potent and specific inhibitor of B-family DNA polymerases, haltering replication and possessing a strong antimitotic activity in human cancer cell lines. Clinical trials revealed limitations of aphidicolin as an antitumor drug because of its low solubility and fast clearance from human plasma. The absence of structural information hampered the improvement of aphidicolin-like inhibitors: more than 50 modifications have been generated so far, but all have lost the inhibitory and antitumor properties. Here we report the crystal structure of the catalytic core of human DNA polymerase alpha (Pol alpha) in the ternary complex with an RNA-primed DNA template and aphidicolin. The inhibitor blocks binding of dCTP by docking at the Pol alpha active site and by rotating the template guanine. The structure provides a plausible mechanism for the selectivity of aphidicolin incorporation opposite template guanine and explains why previous modifications of aphidicolin failed to improve its affinity for Pol alpha. With new structural information, aphidicolin becomes an attractive lead compound for the design of novel derivatives with enhanced inhibitory properties for B-family DNA polymerases.
-
-	Structural basis for inhibition of DNA replication by aphidicolin.,Baranovskiy AG, Babayeva ND, Suwa Y, Gu J, Pavlov YI, Tahirov TH Nucleic Acids Res. 2014 Nov 27. pii: gku1209. PMID:25429975<ref>PMID:25429975</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4q5v" style="background-color:#fffaf0;"></div>

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

OCA at 07:44, 8 February 2023

2023-02-08T07:44:35Z

←Older revision		Revision as of 07:44, 8 February 2023
Line 3:		Line 3:
	<StructureSection load='4q5v' size='340' side='right'caption='[[4q5v]], [[Resolution\|resolution]] 2.52Å' scene=''>		<StructureSection load='4q5v' size='340' side='right'caption='[[4q5v]], [[Resolution\|resolution]] 2.52Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4q5v]] is a 6 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=4Q5V OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4Q5V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4q5v]] is a 6 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=4Q5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q5V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POLA1, POLA ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [https://pdbe.org/4q5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [https://www.ebi.ac.uk/pdbsum/4q5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q5v ProSAT]</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-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [~~http~~://pdbe.org/4q5v PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4q5v PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4q5v ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/DPOLA_HUMAN DPOLA_HUMAN]] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.<ref>PMID:9518481</ref>	+	[https://www.uniprot.org/uniprot/DPOLA_HUMAN DPOLA_HUMAN] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.<ref>PMID:9518481</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
-	*[[DNA polymerase\|DNA polymerase]]	+	*[[DNA polymerase 3D structures\|DNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~DNA-directed DNA polymerase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Babayeva~~, N D~~]]	+	[[Category: Babayeva ND]]
-	[[Category: Baranovskiy~~, A G~~]]	+	[[Category: Baranovskiy AG]]
-	[[Category: Gu, J]]	+	[[Category: Gu J]]
-	[[Category: Suwa, Y]]	+	[[Category: Suwa Y]]
-	[[Category: Tahirov~~, T H]]~~	+	[[Category: Tahirov TH]]
-	~~[[Category: B-family dna polymerase]]~~	+
-	~~[[Category: Dna replication]]~~	+
-	~~[[Category: Transferase-dna-rna complex~~]]	+

OCA at 09:10, 24 April 2019

2019-04-24T09:10:46Z

←Older revision		Revision as of 09:10, 24 April 2019
Line 1:		Line 1:

	==Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex with an RNA-primed DNA template and aphidicolin==		==Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex with an RNA-primed DNA template and aphidicolin==
-	<StructureSection load='4q5v' size='340' side='right' caption='[[4q5v]], [[Resolution\|resolution]] 2.52Å' scene=''>	+	<StructureSection load='4q5v' size='340' side='right'caption='[[4q5v]], [[Resolution\|resolution]] 2.52Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4q5v]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q5V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4q5v]] is a 6 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=4Q5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q5V FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POLA1, POLA ([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-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://pdbe.org/4q5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q5v 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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://pdbe.org/4q5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q5v ProSAT]</span></td></tr>
Line 27:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: DNA-directed DNA polymerase]]		[[Category: DNA-directed DNA polymerase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Babayeva, N D]]		[[Category: Babayeva, N D]]
	[[Category: Baranovskiy, A G]]		[[Category: Baranovskiy, A G]]

OCA at 08:31, 11 August 2016

2016-08-11T08:31:56Z

←Older revision		Revision as of 08:31, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex with an RNA-primed DNA template and aphidicolin==		==Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex with an RNA-primed DNA template and aphidicolin==
	<StructureSection load='4q5v' size='340' side='right' caption='[[4q5v]], [[Resolution\|resolution]] 2.52Å' scene=''>		<StructureSection load='4q5v' size='340' side='right' caption='[[4q5v]], [[Resolution\|resolution]] 2.52Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v 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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://pdbe.org/4q5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q5v ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4q5v" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[DNA polymerase\|DNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 23:00, 24 December 2014

2014-12-24T23:00:20Z

←Older revision		Revision as of 23:00, 24 December 2014
Line 7:		Line 7:
	<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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v 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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DPOLA_HUMAN DPOLA_HUMAN]] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.<ref>PMID:9518481</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:26, 10 December 2014

2014-12-10T11:26:55Z

←Older revision		Revision as of 11:26, 10 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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v 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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v PDBsum]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Natural tetracyclic diterpenoid aphidicolin is a potent and specific inhibitor of B-family DNA polymerases, haltering replication and possessing a strong antimitotic activity in human cancer cell lines. Clinical trials revealed limitations of aphidicolin as an antitumor drug because of its low solubility and fast clearance from human plasma. The absence of structural information hampered the improvement of aphidicolin-like inhibitors: more than 50 modifications have been generated so far, but all have lost the inhibitory and antitumor properties. Here we report the crystal structure of the catalytic core of human DNA polymerase alpha (Pol alpha) in the ternary complex with an RNA-primed DNA template and aphidicolin. The inhibitor blocks binding of dCTP by docking at the Pol alpha active site and by rotating the template guanine. The structure provides a plausible mechanism for the selectivity of aphidicolin incorporation opposite template guanine and explains why previous modifications of aphidicolin failed to improve its affinity for Pol alpha. With new structural information, aphidicolin becomes an attractive lead compound for the design of novel derivatives with enhanced inhibitory properties for B-family DNA polymerases.
		+
		+	Structural basis for inhibition of DNA replication by aphidicolin.,Baranovskiy AG, Babayeva ND, Suwa Y, Gu J, Pavlov YI, Tahirov TH Nucleic Acids Res. 2014 Nov 27. pii: gku1209. PMID:25429975<ref>PMID:25429975</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:13, 26 November 2014

2014-11-26T08:13:01Z

←Older revision		Revision as of 08:13, 26 November 2014
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex with an RNA-primed DNA template and aphidicolin==
-		+	<StructureSection load='4q5v' size='340' side='right' caption='[[4q5v]], [[Resolution\|resolution]] 2.52Å' scene=''>
-	~~The entry~~ 4q5v is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4q5v]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q5V FirstGlance]. <br>
-	~~Authors~~: ~~Baranovskiy~~, A.G., ~~Babayeva~~, N.D., ~~Suwa~~, Y., Gu, J., Tahirov, T.H.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2ZE:(3R,4R,4AR,6AS,8R,9R,11AS,11BS)-4,9-BIS(HYDROXYMETHYL)-4,11B-DIMETHYLTETRADECAHYDRO-8,11A-METHANOCYCLOHEPTA[A]NAPHTHALENE-3,9-DIOL'>2ZE</scene></td></tr>
-		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr>
-	~~Description~~: ~~Crystal structure of the catalytic core of human DNA~~ polymerase ~~alpha in ternary complex with an RNA~~-~~primed DNA template and aphidicolin~~	+	<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=4q5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q5v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q5v RCSB], [http://www.ebi.ac.uk/pdbsum/4q5v PDBsum]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: DNA-directed DNA polymerase]]
		+	[[Category: Babayeva, N D]]
		+	[[Category: Baranovskiy, A G]]
		+	[[Category: Gu, J]]
		+	[[Category: Suwa, Y]]
		+	[[Category: Tahirov, T H]]
		+	[[Category: B-family dna polymerase]]
		+	[[Category: Dna replication]]
		+	[[Category: Transferase-dna-rna complex]]

OCA at 11:18, 19 November 2014

2014-11-19T11:18:37Z

←Older revision		Revision as of 11:18, 19 November 2014
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	Authors: Baranovskiy, A.G., Babayeva, N.D., Suwa, Y., Gu, J., Tahirov, T.H.		Authors: Baranovskiy, A.G., Babayeva, N.D., Suwa, Y., Gu, J., Tahirov, T.H.

-	Description:	+	Description: Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex with an RNA-primed DNA template and aphidicolin

OCA at 06:21, 8 October 2014

2014-10-08T06:21:07Z

←Older revision		Revision as of 06:21, 8 October 2014
Line 3:		Line 3:
	The entry 4q5v is ON HOLD until Paper Publication		The entry 4q5v is ON HOLD until Paper Publication

-	Authors: Baranovskiy, A.G., Babayeva, N.D., Suwa, Y., Gu, J, Tahirov, T.H.	+	Authors: Baranovskiy, A.G., Babayeva, N.D., Suwa, Y., Gu, J., Tahirov, T.H.

	Description:		Description:

OCA at 07:09, 14 May 2014

2014-05-14T07:09:57Z

←Older revision		Revision as of 07:09, 14 May 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4q5v is ON HOLD	+	The entry 4q5v is ON HOLD until Paper Publication

	Authors: Baranovskiy, A.G., Babayeva, N.D., Suwa, Y., Gu, J, Tahirov, T.H.		Authors: Baranovskiy, A.G., Babayeva, N.D., Suwa, Y., Gu, J, Tahirov, T.H.

-	Description: ~~Keep confidential until publication~~	+	Description: