1p62
From Proteopedia
(New page: 200px<br /> <applet load="1p62" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p62, resolution 1.90Å" /> '''Structure of human ...) |
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caption="1p62, resolution 1.90Å" /> | caption="1p62, resolution 1.90Å" /> | ||
'''Structure of human dCK complexed with gemcitabine and ADP-MG'''<br /> | '''Structure of human dCK complexed with gemcitabine and ADP-MG'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1P62 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MG, ADP and GEO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1P62 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=GEO:'>GEO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P62 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: p-loop]] | [[Category: p-loop]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:39:05 2008'' |
Revision as of 14:39, 15 February 2008
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Structure of human dCK complexed with gemcitabine and ADP-MG
Overview
Human deoxycytidine kinase (dCK) phosphorylates the natural, deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and, deoxyadenosine (dA) and is an essential enzyme for the phosphorylation of, numerous nucleoside analog prodrugs routinely used in cancer and antiviral, chemotherapy. For many of these compounds, the phosphorylation step, catalyzed by dCK is the rate-limiting step in their overall activation, pathway. To determine the factors that limit the phosphorylation, efficiency of the prodrug, we solved the crystal structure of dCK to a, resolution of 1.6 A in complex with its physiological substrate, deoxycytidine and with the prodrugs AraC and gemcitabine. The structures, reveal the determinants of dCK substrate specificity. Especially relevant, to new prodrug development is the interaction between Arg128 and the, hydrogen-bond acceptor at the sugar 2'-arabinosyl position of AraC and, gemcitabine. On the basis of the structures, we designed a catalytically, superior dCK variant that could be used in suicide gene-therapy, applications.
About this Structure
1P62 is a Single protein structure of sequence from Mus musculus with , and as ligands. Active as Deoxycytidine kinase, with EC number 2.7.1.74 Full crystallographic information is available from OCA.
Reference
Structure of human dCK suggests strategies to improve anticancer and antiviral therapy., Sabini E, Ort S, Monnerjahn C, Konrad M, Lavie A, Nat Struct Biol. 2003 Jul;10(7):513-9. PMID:12808445
Page seeded by OCA on Fri Feb 15 16:39:05 2008
Categories: Deoxycytidine kinase | Mus musculus | Single protein | Konrad, M. | Lavie, A. | Monnerjahn, C. | Ort, S. | Sabini, E. | ADP | GEO | MG | Gemcitabine | Nucleoside kinase | P-loop
