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2a30

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Revision as of 11:34, 10 September 2015

Crystal structure of human deoxycytidine kinase in complex with deoxycytidine

Structural highlights

2a30 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2a2z
Gene:	DCK (HUMAN)
Activity:	Deoxycytidine kinase, with EC number 2.7.1.74
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Human deoxycytidine kinase (dCK) uses nucleoside triphosphates to phosphorylate several clinically important prodrugs in addition to its natural substrates. Although UTP is the preferred phosphoryl donor for this reaction, our previous studies reported dCK structures solely containing ADP in the phosphoryl donor binding site. To determine the molecular basis of the kinetically observed phosphoryl donor preference, we solved crystal structures of a dCK variant lacking a flexible insert (residues 65-79) but having similar catalytic properties as wild type, in complex with deoxycytidine (dC) and UDP, and in the presence of dC but the absence of UDP or ADP. These structures reveal major changes in the donor base binding loop (residues 240-247) between the UDP-bound and ADP-bound forms, involving significant main-chain rearrangement. This loop is disordered in the dCK-dC structure, which lacks a ligand at the phosphoryl donor site. In comparison with the ADP-bound form, in the presence of UDP this loop is shifted inward to make closer contact to the smaller uracil base. These structures illuminate the phosphoryl donor binding and preference mechanisms of dCK.

Structural basis for the preference of UTP over ATP in human deoxycytidine kinase: illuminating the role of main-chain reorganization.,Godsey MH, Ort S, Sabini E, Konrad M, Lavie A Biochemistry. 2006 Jan 17;45(2):452-61. PMID:16401075^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sabini E, Hazra S, Ort S, Konrad M, Lavie A. Structural basis for substrate promiscuity of dCK. J Mol Biol. 2008 May 2;378(3):607-21. Epub 2008 Mar 3. PMID:18377927 doi:http://dx.doi.org/10.1016/j.jmb.2008.02.061
↑ Hazra S, Ort S, Konrad M, Lavie A. Structural and kinetic characterization of human deoxycytidine kinase variants able to phosphorylate 5-substituted deoxycytidine and thymidine analogues . Biochemistry. 2010 Aug 10;49(31):6784-90. PMID:20614893 doi:10.1021/bi100839e
↑ Godsey MH, Ort S, Sabini E, Konrad M, Lavie A. Structural basis for the preference of UTP over ATP in human deoxycytidine kinase: illuminating the role of main-chain reorganization. Biochemistry. 2006 Jan 17;45(2):452-61. PMID:16401075 doi:http://dx.doi.org/10.1021/bi0518646

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2a30"

@@ Line 2: / Line 2: @@
 <StructureSection load='2a30' size='340' side='right' caption='[[2a30]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2a30]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A30 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A30 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2a30]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A30 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A30 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DCZ:2-DEOXYCYTIDINE'>DCZ</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2a2z|2a2z]]</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 Homo sapiens])</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=2a30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a30 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2a30 RCSB], [http://www.ebi.ac.uk/pdbsum/2a30 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=2a30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a30 OCA], [http://pdbe.org/2a30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a30 RCSB], [http://www.ebi.ac.uk/pdbsum/2a30 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2a30" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 37: / Line 38: @@
 </StructureSection>
 [[Category: Deoxycytidine kinase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Godsey, M H]]
 [[Category: Konrad, M]]

2a30

From Proteopedia

Revision as of 11:34, 10 September 2015

Crystal structure of human deoxycytidine kinase in complex with deoxycytidine

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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