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| | <StructureSection load='3prv' size='340' side='right'caption='[[3prv]], [[Resolution|resolution]] 2.69Å' scene=''> | | <StructureSection load='3prv' size='340' side='right'caption='[[3prv]], [[Resolution|resolution]] 2.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3prv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Trycr Trycr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PRV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3prv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PRV FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nucleoside diphosphate kinase B GI: 71667531, Tc00.1047053508707.200 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5693 TRYCR])</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]] 2.69Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase Nucleoside-diphosphate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.6 2.7.4.6] </span></td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3prv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3prv OCA], [https://pdbe.org/3prv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3prv RCSB], [https://www.ebi.ac.uk/pdbsum/3prv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3prv ProSAT]</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=3prv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3prv OCA], [https://pdbe.org/3prv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3prv RCSB], [https://www.ebi.ac.uk/pdbsum/3prv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3prv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q4E256_TRYCC Q4E256_TRYCC] |
| - | Nucleoside diphosphate kinases play a crucial role in the purine-salvage pathway of trypanosomatid protozoa and have been found in the secretome of Leishmania sp., suggesting a function related to host-cell integrity for the benefit of the parasite. Due to their importance for housekeeping functions in the parasite and by prolonging the life of host cells in infection, they become an attractive target for drug discovery and design. In this work, we describe the first structural characterization of nucleoside diphosphate kinases b from trypanosomatid parasites (tNDKbs) providing insights into their oligomerization, stability and structural determinants for nucleotide binding. Crystallographic studies of LmNDKb when complexed with phosphate, AMP and ADP showed that the crucial hydrogen-bonding residues involved in the nucleotide interaction are fully conserved in tNDKbs. Depending on the nature of the ligand, the nucleotide-binding pocket undergoes conformational changes, which leads to different cavity volumes. SAXS experiments showed that tNDKbs, like other eukaryotic NDKs, form a hexamer in solution and their oligomeric state does not rely on the presence of nucleotides or mimetics. Fluorescence-based thermal-shift assays demonstrated slightly higher stability of tNDKbs compared to human NDKb (HsNDKb), which is in agreement with the fact that tNDKbs are secreted and subjected to variations of temperature in the host cells during infection and disease development. Moreover, tNDKbs were stabilized upon nucleotide binding, whereas HsNDKb was not influenced. Contrasts on the surface electrostatic potential around the nucleotide-binding pocket might be a determinant for nucleotide affinity and protein stability differentiation. All these together demonstrated the molecular adaptation of parasite NDKbs in order to exert their biological functions intra-parasite and when secreted by regulating ATP levels of host cells.
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| - | Molecular adaptability of nucleoside diphosphate kinase b from trypanosomatid parasites: stability, oligomerization and structural determinants of nucleotide binding.,Souza TA, Trindade DM, Tonoli CC, Santos CR, Ward RJ, Arni RK, Oliveira AH, Murakami MT Mol Biosyst. 2011 Apr 28. PMID:21528129<ref>PMID:21528129</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3prv" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]] | | *[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nucleoside-diphosphate kinase]] | + | [[Category: Trypanosoma cruzi]] |
| - | [[Category: Trycr]]
| + | [[Category: Murakami MT]] |
| - | [[Category: Murakami, M T]] | + | [[Category: Oliveira AHC]] |
| - | [[Category: Oliveira, A H.C]] | + | [[Category: Santos CR]] |
| - | [[Category: Santos, C R]] | + | [[Category: Souza TACB]] |
| - | [[Category: Souza, T A.C B]] | + | [[Category: Tonoli CCC]] |
| - | [[Category: Tonoli, C C.C]] | + | [[Category: Trindade DM]] |
| - | [[Category: Trindade, D M]] | + | |
| - | [[Category: Alpha-beta-alpha fold]]
| + | |
| - | [[Category: Nucleoside diphosphate kinase b]]
| + | |
| - | [[Category: Secreted]]
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| - | [[Category: Transferase]]
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| - | [[Category: Trypanosomatid]]
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