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| | ==Transition state mimic of nucleoside-diphosphate kinase from borrelia burgdorferi with bound vanadate and adp== | | ==Transition state mimic of nucleoside-diphosphate kinase from borrelia burgdorferi with bound vanadate and adp== |
| - | <StructureSection load='4dz6' size='340' side='right' caption='[[4dz6]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4dz6' size='340' side='right'caption='[[4dz6]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dz6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_35210 Atcc 35210]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DZ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DZ6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dz6]] 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=4DZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DZ6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VN4:OXIDO(DIOXO)VANADIUM'>VN4</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VN4:OXIDO(DIOXO)VANADIUM'>VN4</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4di6|4di6]]</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=4dz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dz6 OCA], [https://pdbe.org/4dz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dz6 RCSB], [https://www.ebi.ac.uk/pdbsum/4dz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dz6 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ndk, BB_0463 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=139 ATCC 35210])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dz6 OCA], [http://pdbe.org/4dz6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dz6 RCSB], [http://www.ebi.ac.uk/pdbsum/4dz6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dz6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [[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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Nucleoside diphosphate kinase|Nucleoside diphosphate kinase]] | + | *[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 35210]] | + | [[Category: Borreliella burgdorferi]] |
| - | [[Category: Nucleoside-diphosphate kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Kinase]]
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| - | [[Category: Niaid]]
| + | |
| - | [[Category: Nucleoside diphosphate kinase]]
| + | |
| - | [[Category: Ssgcid]]
| + | |
| - | [[Category: Transferase]]
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| - | [[Category: Transition state analog]]
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| - | [[Category: Transition state mimic]]
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| - | [[Category: Vanadate]]
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| Structural highlights
Function
[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).
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dumais M, Davies DR, Lin T, Staker BL, Myler PJ, Van Voorhis WC. Structure and analysis of nucleoside diphosphate kinase from Borrelia burgdorferi prepared in a transition-state complex with ADP and vanadate moieties. Acta Crystallogr F Struct Biol Commun. 2018 Jun 1;74(Pt 6):373-384. doi:, 10.1107/S2053230X18007392. Epub 2018 May 31. PMID:29870023 doi:http://dx.doi.org/10.1107/S2053230X18007392
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