1lwx

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[[Image:1lwx.jpg|left|200px]]<br /><applet load="1lwx" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1lwx.jpg|left|200px]]
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caption="1lwx, resolution 2.3&Aring;" />
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'''AZT DIPHOSPHATE BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE'''<br />
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{{Structure
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|PDB= 1lwx |SIZE=350|CAPTION= <scene name='initialview01'>1lwx</scene>, resolution 2.3&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=AZD:3'-AZIDO-3'-DEOXYTHYMIDINE-5'-DIPHOSPHATE'>AZD</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''AZT DIPHOSPHATE BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1LWX 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=MG:'>MG</scene> and <scene name='pdbligand=AZD:'>AZD</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=1LWX OCA].
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1LWX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LWX OCA].
==Reference==
==Reference==
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X-ray analysis of azido-thymidine diphosphate binding to nucleoside diphosphate kinase., Xu Y, Sellam O, Morera S, Sarfati S, Biondi R, Veron M, Janin J, Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7162-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9207061 9207061]
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X-ray analysis of azido-thymidine diphosphate binding to nucleoside diphosphate kinase., Xu Y, Sellam O, Morera S, Sarfati S, Biondi R, Veron M, Janin J, Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7162-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9207061 9207061]
[[Category: Dictyostelium discoideum]]
[[Category: Dictyostelium discoideum]]
[[Category: Nucleoside-diphosphate kinase]]
[[Category: Nucleoside-diphosphate kinase]]
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[[Category: phosphotransferase]]
[[Category: phosphotransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:49:22 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:36:15 2008''

Revision as of 10:36, 20 March 2008


PDB ID 1lwx

Drag the structure with the mouse to rotate
, resolution 2.3Å
Ligands: and
Activity: Nucleoside-diphosphate kinase, with EC number 2.7.4.6
Coordinates: save as pdb, mmCIF, xml



AZT DIPHOSPHATE BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE


Overview

To be effective as antiviral agent, AZT (3'-azido-3'-deoxythymidine) must be converted to a triphosphate derivative by cellular kinases. The conversion is inefficient and, to understand why AZT diphosphate is a poor substrate of nucleoside diphosphate (NDP) kinase, we determined a 2.3-A x-ray structure of a complex with the N119A point mutant of Dictyostelium NDP kinase. It shows that the analog binds at the same site and, except for the sugar ring pucker which is different, binds in the same way as the natural substrate thymidine diphosphate. However, the azido group that replaces the 3'OH of the deoxyribose in AZT displaces a lysine side chain involved in catalysis. Moreover, it is unable to make an internal hydrogen bond to the oxygen bridging the beta- and gamma-phosphate, which plays an important part in phosphate transfer.

About this Structure

1LWX is a Single protein structure of sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA.

Reference

X-ray analysis of azido-thymidine diphosphate binding to nucleoside diphosphate kinase., Xu Y, Sellam O, Morera S, Sarfati S, Biondi R, Veron M, Janin J, Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7162-5. PMID:9207061

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