2a30
From Proteopedia
(New page: 200px<br /> <applet load="2a30" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a30, resolution 3.02Å" /> '''Crystal structure o...) |
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| - | [[Image:2a30.gif|left|200px]]<br /> | + | [[Image:2a30.gif|left|200px]]<br /><applet load="2a30" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2a30, resolution 3.02Å" /> | caption="2a30, resolution 3.02Å" /> | ||
'''Crystal structure of human deoxycytidine kinase in complex with deoxycytidine'''<br /> | '''Crystal structure of human deoxycytidine kinase in complex with deoxycytidine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human deoxycytidine kinase (dCK) uses nucleoside triphosphates to | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2A30 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and DCZ 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:// | + | 2A30 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=DCZ:'>DCZ</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=2A30 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Godsey, M | + | [[Category: Godsey, M H.]] |
[[Category: Konrad, M.]] | [[Category: Konrad, M.]] | ||
[[Category: Lavie, A.]] | [[Category: Lavie, A.]] | ||
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[[Category: nucleoside kinase]] | [[Category: nucleoside kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:23:05 2008'' |
Revision as of 14:23, 21 February 2008
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Crystal structure of human deoxycytidine kinase in complex with deoxycytidine
Overview
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.
About this Structure
2A30 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Deoxycytidine kinase, with EC number 2.7.1.74 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
Page seeded by OCA on Thu Feb 21 16:23:05 2008
Categories: Deoxycytidine kinase | Homo sapiens | Single protein | Godsey, M H. | Konrad, M. | Lavie, A. | Ort, S. | Sabini, E. | CA | DCZ | Nucleoside kinase
