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| | <StructureSection load='4yeg' size='340' side='right'caption='[[4yeg]], [[Resolution|resolution]] 2.23Å' scene=''> | | <StructureSection load='4yeg' size='340' side='right'caption='[[4yeg]], [[Resolution|resolution]] 2.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yeg]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_tularense"_mccoy_and_chapin_1912 "bacterium tularense" mccoy and chapin 1912]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YEG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YEG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yeg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Francisella_tularensis Francisella tularensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YEG FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ppk2, DR80_1140, DR81_590, DR84_1109, DR85_1285, DR86_904, DR87_59 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=263 "Bacterium tularense" McCoy and Chapin 1912])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.23Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polyphosphate_kinase Polyphosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.1 2.7.4.1] </span></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=4yeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yeg OCA], [https://pdbe.org/4yeg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yeg RCSB], [https://www.ebi.ac.uk/pdbsum/4yeg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yeg ProSAT]</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=4yeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yeg OCA], [http://pdbe.org/4yeg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yeg RCSB], [http://www.ebi.ac.uk/pdbsum/4yeg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yeg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q5NEQ5_FRATT Q5NEQ5_FRATT] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacterium tularense mccoy and chapin 1912]] | + | [[Category: Francisella tularensis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Polyphosphate kinase]]
| + | [[Category: Parnell AE]] |
| - | [[Category: Parnell, A E]] | + | [[Category: Roach PL]] |
| - | [[Category: Roach, P L]] | + | |
| - | [[Category: Polyphosphate kinase enzyme]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
Q5NEQ5_FRATT
Publication Abstract from PubMed
The metabolism of polyphosphate is important for the virulence of a wide range of pathogenic bacteria and the enzymes of polyphosphate metabolism have been proposed as an antibacterial target. In the intracellular pathogen Francisella tularensis , the product of the gene FTT1564 has been identified as a polyphosphate kinase from the PPK2 family. The isogenic deletion mutant was defective for intracellular growth in macrophages and was attenuated in mice, indicating an important role for polyphosphate in the virulence of Francisella . Herein we report the biochemical and structural characterization of F. tularensis polyphosphate kinase ( Ft PPK2) with a view to characterizing the enzyme as a novel target for inhibitors. Using an HPLC based activity assay the substrate specificity of Ft PPK2 was found to include purine but not pyrimidine nucleotides. The activity was also measured using 31P NMR. Ft PPK2 has been crystallized and the structure determined to 2.23 A resolution. The structure consists of a 6- stranded parallel beta sheet surrounded by 12 alpha helices, with a high degree of similarity to other members of the PPK2 family and the thymidylate kinase superfamily. Residues proposed to be important for substrate binding and catalysis have been identified in the structure, including a lid-loop and the conserved Walker A and B motifs. The DeltaFTT1564 strain showed significantly increased sensitivity to a range of antibiotics in a manner independent of the mode of action of the antibiotic. This combination of biochemical, structural and microbiological data provide a sound foundation for future studies targeting the development of PPK2 small molecule inhibitors.
Biochemical and Structural Characterization of Polyphosphate Kinase 2 from the Intracellular Pathogen Francisella tularensis.,Batten LE, Parnell AE, Wells NJ, Murch AL, Oyston PC, Roach PL Biosci Rep. 2015 Nov 18. pii: BSR20150203. PMID:26582818[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Batten LE, Parnell AE, Wells NJ, Murch AL, Oyston PC, Roach PL. Biochemical and Structural Characterization of Polyphosphate Kinase 2 from the Intracellular Pathogen Francisella tularensis. Biosci Rep. 2015 Nov 18. pii: BSR20150203. PMID:26582818 doi:http://dx.doi.org/10.1042/BSR20150203
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