1s5z
From Proteopedia
(New page: 200px<br /><applet load="1s5z" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s5z, resolution 2.Å" /> '''NDP kinase in complex ...) |
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| - | [[Image:1s5z.gif|left|200px]]<br /><applet load="1s5z" size=" | + | [[Image:1s5z.gif|left|200px]]<br /><applet load="1s5z" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1s5z, resolution 2.Å" /> | caption="1s5z, resolution 2.Å" /> | ||
'''NDP kinase in complex with adenosine phosphonoacetic acid'''<br /> | '''NDP kinase in complex with adenosine phosphonoacetic acid'''<br /> | ||
==Overview== | ==Overview== | ||
| - | NDP kinase catalyzes the last step in the phosphorylation of nucleotides. | + | NDP kinase catalyzes the last step in the phosphorylation of nucleotides. It is also involved in the activation by cellular kinases of nucleoside analogs used in antiviral therapies. Adenosine phosphonoacetic acid, a close analog of ADP already proposed as an inhibitor of ribonucleotide reductase, was found to be a poor substrate for human NDP kinase, as well as a weak inhibitor with an equilibrium dissociation constant of 0.6 mM to be compared to 0.025 mM for ADP. The X-ray structure of a complex of adenosine phosphonoacetic acid and the NDP kinase from Dictyostelium was determined to 2.0 A resolution showing that the analog adopts a binding mode similar to ADP, but that no magnesium ion is present at the active site. As ACP may also interfere with other cellular kinases, its potential as a drug targeting NDP kinase or ribonucleotide reductase is likely to be limited due to strong side effects. The design of new molecules with a narrower specificity and a stronger affinity will benefit from the detailed knowledge of the complex ACP-NDP kinase. |
==About this Structure== | ==About this Structure== | ||
| - | 1S5Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum] with PO4 and SON as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase Nucleoside-diphosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.6 2.7.4.6] Full crystallographic information is available from [http:// | + | 1S5Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=SON:'>SON</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase Nucleoside-diphosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.6 2.7.4.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S5Z OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:58:23 2008'' |
Revision as of 12:58, 21 February 2008
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NDP kinase in complex with adenosine phosphonoacetic acid
Overview
NDP kinase catalyzes the last step in the phosphorylation of nucleotides. It is also involved in the activation by cellular kinases of nucleoside analogs used in antiviral therapies. Adenosine phosphonoacetic acid, a close analog of ADP already proposed as an inhibitor of ribonucleotide reductase, was found to be a poor substrate for human NDP kinase, as well as a weak inhibitor with an equilibrium dissociation constant of 0.6 mM to be compared to 0.025 mM for ADP. The X-ray structure of a complex of adenosine phosphonoacetic acid and the NDP kinase from Dictyostelium was determined to 2.0 A resolution showing that the analog adopts a binding mode similar to ADP, but that no magnesium ion is present at the active site. As ACP may also interfere with other cellular kinases, its potential as a drug targeting NDP kinase or ribonucleotide reductase is likely to be limited due to strong side effects. The design of new molecules with a narrower specificity and a stronger affinity will benefit from the detailed knowledge of the complex ACP-NDP kinase.
About this Structure
1S5Z is a Single protein structure of sequence from Dictyostelium discoideum with and as ligands. Active as Nucleoside-diphosphate kinase, with EC number 2.7.4.6 Full crystallographic information is available from OCA.
Reference
Adenosine phosphonoacetic acid is slowly metabolized by NDP kinase., Chen Y, Morera S, Pasti C, Angusti A, Solaroli N, Veron M, Janin J, Manfredini S, Deville-Bonne D, Med Chem. 2005 Nov;1(6):529-36. PMID:16787337
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