1p62

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{{STRUCTURE_1p62| PDB=1p62 | SCENE= }}
{{STRUCTURE_1p62| PDB=1p62 | SCENE= }}
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'''Structure of human dCK complexed with gemcitabine and ADP-MG'''
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===Structure of human dCK complexed with gemcitabine and ADP-MG===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12808445 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12808445}}
==About this Structure==
==About this Structure==
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[[Category: Nucleoside kinase]]
[[Category: Nucleoside kinase]]
[[Category: P-loop]]
[[Category: P-loop]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:43:53 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 02:53:51 2008''

Revision as of 23:53, 27 July 2008

Image:1p62.png

Template:STRUCTURE 1p62

Structure of human dCK complexed with gemcitabine and ADP-MG

Template:ABSTRACT PUBMED 12808445

About this Structure

1P62 is a Single protein structure of sequence from Mus musculus. 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 Mon Jul 28 02:53:51 2008

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