4jlm - Revision history

OCA at 12:04, 1 March 2024

OCA — Fri, 01 Mar 2024 12:04:46 GMT

←Older revision		Revision as of 12:04, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4jlm]] is a 2 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=4JLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JLM FirstGlance]. <br>		<table><tr><td colspan='2'>[[4jlm]] is a 2 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=4JLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JLM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1NN:2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE'>1NN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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]] 2.18Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1NN:2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE'>1NN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [https://pdbe.org/4jlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [https://www.ebi.ac.uk/pdbsum/4jlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jlm 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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [https://pdbe.org/4jlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [https://www.ebi.ac.uk/pdbsum/4jlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jlm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>		[https://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Deoxycytidine kinase (dCK) is a key enzyme in the nucleoside salvage pathway that is also required for the activation of several anticancer and antiviral nucleoside analog prodrugs. Additionally, dCK has been implicated in immune disorders and has been found to be overexpressed in several cancers. To allow the probing and modulation of dCK activity, a new class of small-molecule inhibitors of the enzyme were developed. Here, the structural characterization of four of these inhibitors in complex with human dCK is presented. The structures reveal that the compounds occupy the nucleoside-binding site and bind to the open form of dCK. Surprisingly, a slight variation in the nature of the substituent at the 5-position of the thiazole ring governs whether the active site of the enzyme is occupied by one or two inhibitor molecules. Moreover, this substituent plays a critical role in determining the affinity, improving it from >700 to 1.5 nM in the best binder. These structures lay the groundwork for future modifications that would result in even tighter binding and the correct placement of moieties that confer favorable pharmacodynamics and pharmacokinetic properties.
-
-	Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules.,Nomme J, Murphy JM, Su Y, Sansone ND, Armijo AL, Olson ST, Radu C, Lavie A Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):68-78. doi:, 10.1107/S1399004713025030. Epub 2013 Dec 24. PMID:24419380<ref>PMID:24419380</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4jlm" style="background-color:#fffaf0;"></div>

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

OCA at 11:20, 24 November 2022

OCA — Thu, 24 Nov 2022 11:20:34 GMT

←Older revision		Revision as of 11:20, 24 November 2022
Line 1:		Line 1:

	==Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)==		==Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)==
-	<StructureSection load='4jlm' size='340' side='right' caption='[[4jlm]], [[Resolution\|resolution]] 2.18Å' scene=''>	+	<StructureSection load='4jlm' size='340' side='right'caption='[[4jlm]], [[Resolution\|resolution]] 2.18Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4jlm]] is a 2 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=4JLM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4JLM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4jlm]] is a 2 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=4JLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JLM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1NN:2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE'>1NN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1NN:2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE'>1NN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jlj\|4jlj]], [[4jlk\|4jlk]], [[4jln\|4jln]]</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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [https://pdbe.org/4jlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [https://www.ebi.ac.uk/pdbsum/4jlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jlm ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DCK ([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/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] </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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [~~http~~://pdbe.org/4jlm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4jlm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4jlm ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN]] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>	+	[https://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Deoxycytidine kinase\|Deoxycytidine kinase]]	+	*[[Deoxycytidine kinase 3D structures\|Deoxycytidine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Deoxycytidine kinase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Lavie, A]]	+	[[Category: Lavie A]]
-	[[Category: Nomme, J]]	+	[[Category: Nomme J]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Phosphoryl transfer]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 09:53, 5 August 2016

OCA — Fri, 05 Aug 2016 09:53:21 GMT

←Older revision		Revision as of 09:53, 5 August 2016
Line 1:		Line 1:
		+
	==Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)==		==Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)==
	<StructureSection load='4jlm' size='340' side='right' caption='[[4jlm]], [[Resolution\|resolution]] 2.18Å' scene=''>		<StructureSection load='4jlm' size='340' side='right' caption='[[4jlm]], [[Resolution\|resolution]] 2.18Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DCK ([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/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] </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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [http://www.ebi.ac.uk/pdbsum/4jlm 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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [http://pdbe.org/4jlm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [http://www.ebi.ac.uk/pdbsum/4jlm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jlm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 4jlm" style="background-color:#fffaf0;"></div>

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

OCA at 01:21, 25 December 2014

OCA — Thu, 25 Dec 2014 01:21:56 GMT

←Older revision		Revision as of 01:21, 25 December 2014
Line 9:		Line 9:
	<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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [http://www.ebi.ac.uk/pdbsum/4jlm 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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [http://www.ebi.ac.uk/pdbsum/4jlm PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN]] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 18:25, 21 December 2014

OCA — Sun, 21 Dec 2014 18:25:14 GMT

←Older revision		Revision as of 18:25, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4jlm\| PDB=4jlm \| SCENE= }}~~	+	==Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)==
-	===Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)===	+	<StructureSection load='4jlm' size='340' side='right' caption='[[4jlm]], [[Resolution\|resolution]] 2.18Å' scene=''>
-	{~~{ABSTRACT_PUBMED_24419380}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4jlm]] is a 2 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=4JLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JLM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1NN:2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE'>1NN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jlj\|4jlj]], [[4jlk\|4jlk]], [[4jln\|4jln]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DCK ([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/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] </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=4jlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jlm RCSB], [http://www.ebi.ac.uk/pdbsum/4jlm PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Deoxycytidine kinase (dCK) is a key enzyme in the nucleoside salvage pathway that is also required for the activation of several anticancer and antiviral nucleoside analog prodrugs. Additionally, dCK has been implicated in immune disorders and has been found to be overexpressed in several cancers. To allow the probing and modulation of dCK activity, a new class of small-molecule inhibitors of the enzyme were developed. Here, the structural characterization of four of these inhibitors in complex with human dCK is presented. The structures reveal that the compounds occupy the nucleoside-binding site and bind to the open form of dCK. Surprisingly, a slight variation in the nature of the substituent at the 5-position of the thiazole ring governs whether the active site of the enzyme is occupied by one or two inhibitor molecules. Moreover, this substituent plays a critical role in determining the affinity, improving it from >700 to 1.5 nM in the best binder. These structures lay the groundwork for future modifications that would result in even tighter binding and the correct placement of moieties that confer favorable pharmacodynamics and pharmacokinetic properties.

-	~~==Function==~~	+	Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules.,Nomme J, Murphy JM, Su Y, Sansone ND, Armijo AL, Olson ST, Radu C, Lavie A Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):68-78. doi:, 10.1107/S1399004713025030. Epub 2013 Dec 24. PMID:24419380<ref>PMID:24419380</ref>
-	~~[[http://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN]] Required for~~ the ~~phosphorylation~~ of the ~~deoxyribonucleosides deoxycytidine (dC)~~, ~~deoxyguanosine~~ (~~dG) and deoxyadenosine (dA~~). ~~Has broad substrate specificity~~, ~~and does not display selectivity based on the chirality of the substrate~~. ~~It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents~~.~~<ref>~~PMID:~~18377927</ref>~~ <ref>PMID:~~20614893~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4jlm]] is~~ a ~~2 chain structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4JLM OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:024419380</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Deoxycytidine kinase\|Deoxycytidine kinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Deoxycytidine kinase]]		[[Category: Deoxycytidine kinase]]
-	[[Category: Lavie, A.]]	+	[[Category: Human]]
-	[[Category: Nomme, J.]]	+	[[Category: Lavie, A]]
		+	[[Category: Nomme, J]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Phosphoryl transfer]]		[[Category: Phosphoryl transfer]]
	[[Category: Phosphorylation]]		[[Category: Phosphorylation]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 14:15, 19 February 2014

OCA — Wed, 19 Feb 2014 14:15:39 GMT

←Older revision		Revision as of 14:15, 19 February 2014
Line 1:		Line 1:
	{{STRUCTURE_4jlm\| PDB=4jlm \| SCENE= }}		{{STRUCTURE_4jlm\| PDB=4jlm \| SCENE= }}
	===Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)===		===Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)===
		+	{{ABSTRACT_PUBMED_24419380}}

	==Function==		==Function==
Line 9:		Line 10:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:024419380</ref><references group="xtra"/><references/>
	[[Category: Deoxycytidine kinase]]		[[Category: Deoxycytidine kinase]]
	[[Category: Lavie, A.]]		[[Category: Lavie, A.]]

OCA at 07:03, 22 January 2014

OCA — Wed, 22 Jan 2014 07:03:23 GMT

←Older revision		Revision as of 07:03, 22 January 2014
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-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4jlm\| PDB=4jlm \| SCENE= }}
		+	===Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)===

-	~~The entry 4jlm~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN]] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>

-	~~Authors~~: ~~Nomme, J~~.~~, Lavie, A~~.	+	==About this Structure==
		+	[[4jlm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JLM OCA].

-	~~Description~~: ~~Human dCK C4S-S74E mutant in complex with UDP and the F2~~.3.~~1 inhibitor (2-~~[~~({5-ETHYL-2-~~[~~3-(2-FLUOROETHOXY)-4-METHOXYPHENYL~~]~~-1,3-THIAZOL-4-YL}METHYL)SULFANYL~~]~~PYRIMIDINE~~-~~4,6-DIAMINE)~~	+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Deoxycytidine kinase]]
		+	[[Category: Lavie, A.]]
		+	[[Category: Nomme, J.]]
		+	[[Category: Kinase]]
		+	[[Category: Phosphoryl transfer]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 19:55, 17 April 2013

OCA — Wed, 17 Apr 2013 19:55:33 GMT

←Older revision		Revision as of 19:55, 17 April 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Nomme, J., Lavie, A.		Authors: Nomme, J., Lavie, A.

-	Description: Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor	+	Description: Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor (2-[({5-ETHYL-2-[3-(2-FLUOROETHOXY)-4-METHOXYPHENYL]-1,3-THIAZOL-4-YL}METHYL)SULFANYL]PYRIMIDINE-4,6-DIAMINE)

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

OCA — Wed, 20 Mar 2013 16:22:35 GMT

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

←Older revision

Revision as of 16:22, 20 March 2013

OCA: New page: '''Unreleased structure''' The entry 4jlm is ON HOLD Authors: Nomme, J., Lavie, A. Description: Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor

OCA — Wed, 20 Mar 2013 16:22:34 GMT

New page: '''Unreleased structure''' The entry 4jlm is ON HOLD Authors: Nomme, J., Lavie, A. Description: Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor

New page

'''Unreleased structure'''

The entry 4jlm is ON HOLD

Authors: Nomme, J., Lavie, A.

Description: Human dCK C4S-S74E mutant in complex with UDP and the F2.3.1 inhibitor