4di6: Difference between revisions
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==crystal structure of nucleoside-diphosphate kinase from Borrelia burgdorferi== | |||
<StructureSection load='4di6' size='340' side='right'caption='[[4di6]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4di6]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Borreliella_burgdorferi Borreliella burgdorferi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DI6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DI6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4di6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4di6 OCA], [https://pdbe.org/4di6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4di6 RCSB], [https://www.ebi.ac.uk/pdbsum/4di6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4di6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NDK_BORBU NDK_BORBU] Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Nucleoside diphosphate kinases (NDKs) are implicated in a wide variety of cellular functions owing to their enzymatic conversion of NDP to NTP. NDK from Borrelia burgdorferi (BbNDK) was selected for functional and structural analysis to determine whether its activity is required for infection and to assess its potential for therapeutic inhibition. The Seattle Structural Genomics Center for Infectious Diseases (SSGCID) expressed recombinant BbNDK protein. The protein was crystallized and structures were solved of both the apoenzyme and a liganded form with ADP and vanadate ligands. This provided two structures and allowed the elucidation of changes between the apo and ligand-bound enzymes. Infectivity studies with ndk transposon mutants demonstrated that NDK function was important for establishing a robust infection in mice, and provided a rationale for therapeutic targeting of BbNDK. The protein structure was compared with other NDK structures found in the Protein Data Bank and was found to have similar primary, secondary, tertiary and quaternary structures, with conserved residues acting as the catalytic pocket, primarily using His132 as the phosphohistidine-transfer residue. Vanadate and ADP complexes model the transition state of this phosphoryl-transfer reaction, demonstrating that the pocket closes when bound to ADP, while allowing the addition or removal of a gamma-phosphate. This analysis provides a framework for the design of potential therapeutics targeting BbNDK inhibition. | |||
Structure and analysis of nucleoside diphosphate kinase from Borrelia burgdorferi prepared in a transition-state complex with ADP and vanadate moieties.,Dumais M, Davies DR, Lin T, Staker BL, Myler PJ, Van Voorhis WC Acta Crystallogr F Struct Biol Commun. 2018 Jun 1;74(Pt 6):373-384. doi:, 10.1107/S2053230X18007392. Epub 2018 May 31. PMID:29870023<ref>PMID:29870023</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4di6" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Nucleoside diphosphate kinase|Nucleoside diphosphate kinase]] | *[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: | [[Category: Borreliella burgdorferi]] | ||
[[Category: Large Structures]] | |||
[[Category: | |||
Latest revision as of 09:53, 27 November 2024
crystal structure of nucleoside-diphosphate kinase from Borrelia burgdorfericrystal structure of nucleoside-diphosphate kinase from Borrelia burgdorferi
Structural highlights
FunctionNDK_BORBU Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). Publication Abstract from PubMedNucleoside diphosphate kinases (NDKs) are implicated in a wide variety of cellular functions owing to their enzymatic conversion of NDP to NTP. NDK from Borrelia burgdorferi (BbNDK) was selected for functional and structural analysis to determine whether its activity is required for infection and to assess its potential for therapeutic inhibition. The Seattle Structural Genomics Center for Infectious Diseases (SSGCID) expressed recombinant BbNDK protein. The protein was crystallized and structures were solved of both the apoenzyme and a liganded form with ADP and vanadate ligands. This provided two structures and allowed the elucidation of changes between the apo and ligand-bound enzymes. Infectivity studies with ndk transposon mutants demonstrated that NDK function was important for establishing a robust infection in mice, and provided a rationale for therapeutic targeting of BbNDK. The protein structure was compared with other NDK structures found in the Protein Data Bank and was found to have similar primary, secondary, tertiary and quaternary structures, with conserved residues acting as the catalytic pocket, primarily using His132 as the phosphohistidine-transfer residue. Vanadate and ADP complexes model the transition state of this phosphoryl-transfer reaction, demonstrating that the pocket closes when bound to ADP, while allowing the addition or removal of a gamma-phosphate. This analysis provides a framework for the design of potential therapeutics targeting BbNDK inhibition. Structure and analysis of nucleoside diphosphate kinase from Borrelia burgdorferi prepared in a transition-state complex with ADP and vanadate moieties.,Dumais M, Davies DR, Lin T, Staker BL, Myler PJ, Van Voorhis WC Acta Crystallogr F Struct Biol Commun. 2018 Jun 1;74(Pt 6):373-384. doi:, 10.1107/S2053230X18007392. Epub 2018 May 31. PMID:29870023[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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