1lwx

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[[Image:1lwx.jpg|left|200px]]
[[Image:1lwx.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1lwx |SIZE=350|CAPTION= <scene name='initialview01'>1lwx</scene>, resolution 2.3&Aring;
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The line below this paragraph, containing "STRUCTURE_1lwx", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=AZD:3&#39;-AZIDO-3&#39;-DEOXYTHYMIDINE-5&#39;-DIPHOSPHATE'>AZD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1lwx| PDB=1lwx | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lwx OCA], [http://www.ebi.ac.uk/pdbsum/1lwx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lwx RCSB]</span>
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}}
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'''AZT DIPHOSPHATE BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE'''
'''AZT DIPHOSPHATE BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE'''
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[[Category: Janin, J.]]
[[Category: Janin, J.]]
[[Category: Xu, Y.]]
[[Category: Xu, Y.]]
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[[Category: antiviral agent]]
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[[Category: Antiviral agent]]
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[[Category: azidothymidine]]
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[[Category: Azidothymidine]]
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[[Category: phosphotransferase]]
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[[Category: Phosphotransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:23:04 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:08:27 2008''
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Revision as of 21:23, 2 May 2008

Image:1lwx.jpg

Template:STRUCTURE 1lwx

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 Page seeded by OCA on Sat May 3 00:23:04 2008

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OCA

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