1mn7: Difference between revisions
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==NDP kinase mutant (H122G;N119S;F64W) in complex with aBAZTTP== | ==NDP kinase mutant (H122G;N119S;F64W) in complex with aBAZTTP== | ||
<StructureSection load='1mn7' size='340' side='right' caption='[[1mn7]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='1mn7' size='340' side='right'caption='[[1mn7]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1mn7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_11735 Atcc 11735]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MN7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MN7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[1mn7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_11735 Atcc 11735]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MN7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MN7 FirstGlance]. <br> | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mn/1mn7_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mn/1mn7_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 1mn7" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1mn7" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Nucleoside diphosphate kinase|Nucleoside diphosphate kinase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Atcc 11735]] | [[Category: Atcc 11735]] | ||
[[Category: Large Structures]] | |||
[[Category: Nucleoside-diphosphate kinase]] | [[Category: Nucleoside-diphosphate kinase]] | ||
[[Category: Chen, y]] | [[Category: Chen, y]] | ||
Revision as of 11:03, 31 July 2019
NDP kinase mutant (H122G;N119S;F64W) in complex with aBAZTTPNDP kinase mutant (H122G;N119S;F64W) in complex with aBAZTTP
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAntiviral nucleoside analog therapies rely on their incorporation by viral DNA polymerases/reverse transcriptase leading to chain termination. The analogs (3'-deoxy-3'-azidothymidine (AZT), 2',3'-didehydro-2',3'-dideoxythymidine (d4T), and other dideoxynucleosides) are sequentially converted into triphosphate by cellular kinases of the nucleoside salvage pathway and are often poor substrates of these enzymes. Nucleoside diphosphate (NDP) kinase phosphorylates the diphosphate derivatives of the analogs with an efficiency some 10(4) lower than for its natural substrates. Kinetic and structural studies of Dictyostelium and human NDP kinases show that the sugar 3'-OH, absent from all antiviral analogs, is required for catalysis. To improve the catalytic efficiency of NDP kinase on the analogs, we engineered several mutants with a protein OH group replacing the sugar 3'-OH. The substitution of Asn-115 in Ser and Leu-55 in His results in an NDP kinase mutant with an enhanced ability to phosphorylate antiviral derivatives. Transfection of the mutant enzyme in Escherichia coli results in an increased sensitivity to AZT. An x-ray structure at 2.15-A resolution of the Dictyostelium enzyme bearing the serine substitution in complex with the R(p)-alpha-borano-triphosphate derivative of AZT shows that the enhanced activity reflects an improved geometry of binding and a favorable interaction of the 3'-azido group with the engineered serine. Improving nucleoside diphosphate kinase for antiviral nucleotide analogs activation.,Gallois-Montbrun S, Schneider B, Chen Y, Giacomoni-Fernandes V, Mulard L, Morera S, Janin J, Deville-Bonne D, Veron M J Biol Chem. 2002 Oct 18;277(42):39953-9. Epub 2002 Aug 8. PMID:12171931[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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