2a2z

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{{STRUCTURE_2a2z| PDB=2a2z | SCENE= }}
{{STRUCTURE_2a2z| PDB=2a2z | SCENE= }}
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'''Crystal Structure of human deoxycytidine kinase in complex with deoxycytidine and uridine diphosphate'''
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===Crystal Structure of human deoxycytidine kinase in complex with deoxycytidine and uridine diphosphate===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16401075 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16401075}}
==About this Structure==
==About this Structure==
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[[Category: Nucleoside kinase]]
[[Category: Nucleoside kinase]]
[[Category: Uridine diphosphate]]
[[Category: Uridine diphosphate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:32:10 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:39:52 2008''

Revision as of 01:39, 28 July 2008

Image:2a2z.png

Template:STRUCTURE 2a2z

Crystal Structure of human deoxycytidine kinase in complex with deoxycytidine and uridine diphosphate

Template:ABSTRACT PUBMED 16401075

About this Structure

2A2Z is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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