4r1r - Revision history

OCA at 12:49, 1 March 2024

OCA — Fri, 01 Mar 2024 12:49:33 GMT

←Older revision		Revision as of 12:49, 1 March 2024
Line 3:		Line 3:
	<StructureSection load='4r1r' size='340' side='right'caption='[[4r1r]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='4r1r' size='340' side='right'caption='[[4r1r]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4r1r]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_coli"_migula_1895 "bacillus~~ coli~~" migula 1895~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R1R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4r1r]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R1R FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GDP:GUANOSINE~~-~~5-DIPHOSPHATE'>GDP</scene>~~, ~~<scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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]] 3.2Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>NRDA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~562~~ "~~Bacillus coli~~" ~~Migula 1895])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Ribonucleoside~~-~~diphosphate_reductase Ribonucleoside~~-~~diphosphate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1]~~ </~~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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [https://pdbe.org/4r1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [https://www.ebi.ac.uk/pdbsum/4r1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r1r 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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [https://pdbe.org/4r1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [https://www.ebi.ac.uk/pdbsum/4r1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r1r ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/RIR1_ECOLI RIR1_ECOLI]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines. [[https://www.uniprot.org/uniprot/RIR2_ECOLI RIR2_ECOLI]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R2 contains the tyrosyl radical required for catalysis.	+	[https://www.uniprot.org/uniprot/RIR1_ECOLI RIR1_ECOLI] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4r1r ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4r1r ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	BACKGROUND: Ribonucleotide reductase (RNR) is an essential enzyme in DNA synthesis, catalyzing all de novo synthesis of deoxyribonucleotides. The enzyme comprises two dimers, termed R1 and R2, and contains the redox active cysteine residues, Cys462 and Cys225. The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals. The pathway for the radical has previously been suggested from crystallographic results, and is supported by site-directed mutagenesis studies. Most RNRs are allosterically regulated through two different nucleotide-binding sites: one site controls general activity and the other controls substrate specificity. Our aim has been to crystallographically demonstrate substrate binding and to locate the two effector-binding sites. RESULTS: We report here the first crystal structure of RNR R1 in a reduced form. The structure shows that upon reduction of the redox active cysteines, the sulfur atom of Cys462 becomes deeply buried. The more accessible Cys225 moves to the former position of Cys462 making room for the substrate. In addition, the structures of R1 in complexes with effector, effector analog and effector plus substrate provide information about these binding sites. The substrate GDP binds in a cleft between two domains with its beta-phosphate bound to the N termini of two helices; the ribose forms hydrogen bonds to conserved residues. Binding of dTTP at the allosteric substrate specificity site stabilizes three loops close to the dimer interface and the active site, whereas the general allosteric binding site is positioned far from the active site. CONCLUSIONS: Binding of substrate at the active site of the enzyme is structurally regulated in two ways: binding of the correct substrate is regulated by the binding of allosteric effectors and binding of the actual substrate occurs primarily when the active-site cysteines are reduced. One of the loops stabilized upon binding of dTTP participates in the formation of the substrate-binding site through direct interaction with the nucleotide base. The general allosteric effector site, located far from the active site, appears to regulate subunit interactions within the holoenzyme.
-
-	Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding.,Eriksson M, Uhlin U, Ramaswamy S, Ekberg M, Regnstrom K, Sjoberg BM, Eklund H Structure. 1997 Aug 15;5(8):1077-92. PMID:9309223<ref>PMID:9309223</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4r1r" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Ribonucleotide reductase 3D structures\|Ribonucleotide reductase 3D structures]]		*[[Ribonucleotide reductase 3D structures\|Ribonucleotide reductase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus~~ coli ~~migula 1895~~]]	+	[[Category: Escherichia coli]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Ribonucleoside-diphosphate reductase]]~~	+	[[Category: Eklund H]]
-	[[Category: Eklund, H]]	+	[[Category: Eriksson M]]
-	[[Category: Eriksson, M]]	+
-	~~[[Category: Allosteric regulation]]~~	+
-	~~[[Category: Deoxyribonucleotide synthesis]]~~	+
-	~~[[Category: Radical chemistry]]~~	+
-	~~[[Category: Ribonucleotide reductase]]~~	+
-	~~[[Category: Specificity~~]]	+

OCA at 15:50, 3 November 2021

OCA — Wed, 03 Nov 2021 15:50:08 GMT

←Older revision		Revision as of 15:50, 3 November 2021
Line 1:		Line 1:
		+
	==RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI==		==RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI==
-	<StructureSection load='4r1r' size='340' side='right' caption='[[4r1r]], [[Resolution\|resolution]] 3.20Å' scene=''>	+	<StructureSection load='4r1r' size='340' side='right'caption='[[4r1r]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4r1r]] is a 7 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4R1R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4r1r]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R1R FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NRDA ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NRDA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] </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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [~~http~~://pdbe.org/4r1r PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4r1r PDBsum]</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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [https://pdbe.org/4r1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [https://www.ebi.ac.uk/pdbsum/4r1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r1r ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/RIR1_ECOLI RIR1_ECOLI]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines. [[~~http~~://www.uniprot.org/uniprot/RIR2_ECOLI RIR2_ECOLI]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R2 contains the tyrosyl radical required for catalysis.	+	[[https://www.uniprot.org/uniprot/RIR1_ECOLI RIR1_ECOLI]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines. [[https://www.uniprot.org/uniprot/RIR2_ECOLI RIR2_ECOLI]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R2 contains the tyrosyl radical required for catalysis.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r1/4r1r_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r1/4r1r_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 31:		Line 32:

	==See Also==		==See Also==
-	*[[Ribonucleotide reductase\|Ribonucleotide reductase]]	+	*[[Ribonucleotide reductase 3D structures\|Ribonucleotide reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 37:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Bacillus coli migula 1895]]		[[Category: Bacillus coli migula 1895]]
		+	[[Category: Large Structures]]
	[[Category: Ribonucleoside-diphosphate reductase]]		[[Category: Ribonucleoside-diphosphate reductase]]
	[[Category: Eklund, H]]		[[Category: Eklund, H]]

OCA at 18:53, 9 February 2016

OCA — Tue, 09 Feb 2016 18:53:19 GMT

←Older revision		Revision as of 18:53, 9 February 2016
Line 2:		Line 2:
	<StructureSection load='4r1r' size='340' side='right' caption='[[4r1r]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='4r1r' size='340' side='right' caption='[[4r1r]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4r1r]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Escherichia_coli Escherichia~~ coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R1R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4r1r]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R1R FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NRDA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 ~~Escherichia~~ coli])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NRDA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] </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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [http://www.ebi.ac.uk/pdbsum/4r1r 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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [http://pdbe.org/4r1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [http://www.ebi.ac.uk/pdbsum/4r1r PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4r1r ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 28:		Line 28:
	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 4r1r" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Escherichia~~ coli]]	+	[[Category: Bacillus coli migula 1895]]
	[[Category: Ribonucleoside-diphosphate reductase]]		[[Category: Ribonucleoside-diphosphate reductase]]
	[[Category: Eklund, H]]		[[Category: Eklund, H]]

OCA at 08:50, 25 December 2014

OCA — Thu, 25 Dec 2014 08:50:05 GMT

←Older revision		Revision as of 08:50, 25 December 2014
Line 8:		Line 8:
	<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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [http://www.ebi.ac.uk/pdbsum/4r1r 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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [http://www.ebi.ac.uk/pdbsum/4r1r PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RIR1_ECOLI RIR1_ECOLI]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines. [[http://www.uniprot.org/uniprot/RIR2_ECOLI RIR2_ECOLI]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R2 contains the tyrosyl radical required for catalysis.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 17:05, 10 December 2014

OCA — Wed, 10 Dec 2014 17:05:55 GMT

←Older revision		Revision as of 17:05, 10 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4r1r.~~png~~\|~~left~~\|200px]]	+	==RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI==
		+	<StructureSection load='4r1r' size='340' side='right' caption='[[4r1r]], [[Resolution\|resolution]] 3.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4r1r]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R1R FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NRDA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] </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=4r1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r1r RCSB], [http://www.ebi.ac.uk/pdbsum/4r1r PDBsum]</span></td></tr>
		+	</table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r1/4r1r_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: Ribonucleotide reductase (RNR) is an essential enzyme in DNA synthesis, catalyzing all de novo synthesis of deoxyribonucleotides. The enzyme comprises two dimers, termed R1 and R2, and contains the redox active cysteine residues, Cys462 and Cys225. The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals. The pathway for the radical has previously been suggested from crystallographic results, and is supported by site-directed mutagenesis studies. Most RNRs are allosterically regulated through two different nucleotide-binding sites: one site controls general activity and the other controls substrate specificity. Our aim has been to crystallographically demonstrate substrate binding and to locate the two effector-binding sites. RESULTS: We report here the first crystal structure of RNR R1 in a reduced form. The structure shows that upon reduction of the redox active cysteines, the sulfur atom of Cys462 becomes deeply buried. The more accessible Cys225 moves to the former position of Cys462 making room for the substrate. In addition, the structures of R1 in complexes with effector, effector analog and effector plus substrate provide information about these binding sites. The substrate GDP binds in a cleft between two domains with its beta-phosphate bound to the N termini of two helices; the ribose forms hydrogen bonds to conserved residues. Binding of dTTP at the allosteric substrate specificity site stabilizes three loops close to the dimer interface and the active site, whereas the general allosteric binding site is positioned far from the active site. CONCLUSIONS: Binding of substrate at the active site of the enzyme is structurally regulated in two ways: binding of the correct substrate is regulated by the binding of allosteric effectors and binding of the actual substrate occurs primarily when the active-site cysteines are reduced. One of the loops stabilized upon binding of dTTP participates in the formation of the substrate-binding site through direct interaction with the nucleotide base. The general allosteric effector site, located far from the active site, appears to regulate subunit interactions within the holoenzyme.

-	~~{{STRUCTURE_4r1r\| PDB=4r1r \| SCENE= }}~~	+	Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding.,Eriksson M, Uhlin U, Ramaswamy S, Ekberg M, Regnstrom K, Sjoberg BM, Eklund H Structure. 1997 Aug 15;5(8):1077-92. PMID:9309223<ref>PMID:9309223</ref>

-	~~===RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE~~, ~~GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_9309223}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[4r1r]] is~~ a ~~7 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Escherichia_coli Escherichia coli]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA].~~	+

	==See Also==		==See Also==
	*[[Ribonucleotide reductase\|Ribonucleotide reductase]]		*[[Ribonucleotide reductase\|Ribonucleotide reductase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:009309223<~~/~~ref~~><~~ref group="xtra">PMID:017486094</ref><references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]
	[[Category: Ribonucleoside-diphosphate reductase]]		[[Category: Ribonucleoside-diphosphate reductase]]
-	[[Category: Eklund, H.]]	+	[[Category: Eklund, H]]
-	[[Category: Eriksson, M.]]	+	[[Category: Eriksson, M]]
	[[Category: Allosteric regulation]]		[[Category: Allosteric regulation]]
	[[Category: Deoxyribonucleotide synthesis]]		[[Category: Deoxyribonucleotide synthesis]]

OCA at 14:48, 20 October 2012

OCA — Sat, 20 Oct 2012 14:48:33 GMT

←Older revision		Revision as of 14:48, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[4r1r]] is a 7 chain structure ~~of [[Ribonucleotide reductase]]~~ with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA].	+	[[4r1r]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA].

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

OCA: Protected "4r1r" [edit=sysop:move=sysop]

OCA — Thu, 26 Jul 2012 16:19:32 GMT

Protected "4r1r" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:19, 26 July 2012

OCA at 16:19, 26 July 2012

OCA — Thu, 26 Jul 2012 16:19:30 GMT

←Older revision		Revision as of 16:19, 26 July 2012
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-	{{Seed}}
	[[Image:4r1r.png\|left\|200px]]		[[Image:4r1r.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_4r1r", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_4r1r\| PDB=4r1r \| SCENE= }}		{{STRUCTURE_4r1r\| PDB=4r1r \| SCENE= }}

	===RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI===		===RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_9309223}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 9309223 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_9309223}}		{{ABSTRACT_PUBMED_9309223}}

	==About this Structure==		==About this Structure==
-	~~4R1R~~ is a 7 ~~chains~~ structure of ~~sequences~~ from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA].	+	[[4r1r]] is a 7 chain structure of [[Ribonucleotide reductase]] with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA].
		+
		+	==See Also==
		+	*[[Ribonucleotide reductase\|Ribonucleotide reductase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~9309223~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:009309223</ref><ref group="xtra">PMID:017486094</ref><references group="xtra"/>
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]
	[[Category: Ribonucleoside-diphosphate reductase]]		[[Category: Ribonucleoside-diphosphate reductase]]
Line 33:		Line 24:
	[[Category: Ribonucleotide reductase]]		[[Category: Ribonucleotide reductase]]
	[[Category: Specificity]]		[[Category: Specificity]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 11:59:50 2009''

OCA at 09:59, 17 February 2009

OCA — Tue, 17 Feb 2009 09:59:51 GMT

←Older revision		Revision as of 09:59, 17 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	4R1R is a ~~[[Protein complex]]~~ structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA].	+	4R1R is a 7 chains structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA].

	==Reference==		==Reference==
-	Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding., Eriksson M, Uhlin U, Ramaswamy S, Ekberg M, Regnstrom K, Sjoberg BM, Eklund H, Structure. 1997 Aug 15;5(8):1077-92. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/9309223 9309223]~~	+	<ref group="xtra">PMID:9309223</ref><references group="xtra"/>
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]
-	[[Category: Protein complex]]
	[[Category: Ribonucleoside-diphosphate reductase]]		[[Category: Ribonucleoside-diphosphate reductase]]
	[[Category: Eklund, H.]]		[[Category: Eklund, H.]]
Line 35:		Line 34:
	[[Category: Specificity]]		[[Category: Specificity]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Jul 3 13~~:48:~~27 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 11:59:50 2009''

OCA at 10:48, 3 July 2008

OCA — Thu, 03 Jul 2008 10:48:28 GMT

←Older revision		Revision as of 10:48, 3 July 2008
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-	[[Image:4r1r.~~gif~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:4r1r.png\|left\|200px]]

	<!--		<!--
Line 9:		Line 10:
	{{STRUCTURE_4r1r\| PDB=4r1r \| SCENE= }}		{{STRUCTURE_4r1r\| PDB=4r1r \| SCENE= }}

-	~~'''~~RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI~~'''~~	+	===RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI===


-	~~==Overview==~~	+	<!--
-	~~BACKGROUND: Ribonucleotide reductase (RNR) is an essential enzyme in DNA synthesis, catalyzing all de novo synthesis of deoxyribonucleotides.~~ The ~~enzyme comprises two dimers~~, ~~termed R1 and R2~~, ~~and contains~~ the ~~redox active cysteine residues, Cys462 and Cys225. The reduction of ribonucleotides~~ to ~~deoxyribonucleotides involves~~ the transfer of free radicals. The pathway for the radical has previously been suggested from crystallographic results, and is supported by site-directed mutagenesis studies. Most RNRs are allosterically regulated through two different nucleotide-binding sites: ~~one site controls general activity and the other controls substrate specificity~~. ~~Our aim has been to crystallographically demonstrate substrate binding and to locate the two effector-binding sites~~. ~~RESULTS: We report here the first crystal structure of RNR R1 in a reduced form. The structure shows that upon reduction of the redox active cysteines~~, the sulfur atom of Cys462 becomes deeply buried. The more accessible Cys225 moves to the former position of Cys462 making room for the substrate. In addition, the structures of R1 in complexes with effector, effector analog and effector plus substrate provide information about these binding sites. The substrate GDP binds in a cleft between two domains with its beta-phosphate bound to the N termini of two helices; the ribose forms hydrogen bonds to conserved residues. Binding of dTTP at the allosteric substrate specificity site stabilizes three loops close to the dimer interface and the active site, whereas the general allosteric binding site is ~~positioned far from~~ the ~~active site~~. CONCLUSIONS: Binding of substrate at the active site of the enzyme is structurally regulated in two ways: binding of the correct substrate is regulated by the binding of allosteric effectors and binding of the actual substrate occurs primarily when the active-~~site cysteines are reduced. One of the loops stabilized upon binding of dTTP participates in the formation of the substrate~~-binding site through direct interaction with the nucleotide base. The general allosteric effector site, located far from the active site, appears to regulate subunit interactions within the holoenzyme.	+	The line below this paragraph, {{ABSTRACT_PUBMED_9309223}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 9309223 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_9309223}}

	==About this Structure==		==About this Structure==
Line 30:		Line 34:
	[[Category: Ribonucleotide reductase]]		[[Category: Ribonucleotide reductase]]
	[[Category: Specificity]]		[[Category: Specificity]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun May~~ ~~4 22~~:28:33 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 13:48:27 2008''