3q83: Difference between revisions
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==Crystal structure of Staphylococcus aureus nucleoside diphosphate kinase== | |||
=== | <StructureSection load='3q83' size='340' side='right' caption='[[3q83]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3q83]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_col Staphylococcus aureus subsp. aureus col]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q83 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q83 FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3q86|3q86]], [[3q89|3q89]], [[3q8u|3q8u]], [[3q8v|3q8v]], [[3q8y|3q8y]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ndk, SACOL1509 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=93062 Staphylococcus aureus subsp. aureus COL])</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=3q83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q83 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q83 RCSB], [http://www.ebi.ac.uk/pdbsum/3q83 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Nucleoside diphosphate kinases (NDK) are characterized by high catalytic turnover rates and diverse substrate specificity. These features make this enzyme an effective activator of a pro-drug-an application that has been actively pursued for a variety of therapeutic strategies. The catalytic mechanism of this enzyme is governed by a conserved histidine that coordinates a magnesium ion at the active site. Despite substantial structural and biochemical information on NDK, the mechanistic feature of the phospho-transfer that leads to auto-phosphorylation remains unclear. While the role of the histidine residue is well documented, the other active site residues, in particular the conserved serine remains poorly characterized. Studies on some homologues suggest no role for the serine residue at the active site, while others suggest a crucial role for this serine in the regulation and quaternary association of this enzyme in some species. Here we report the biochemical features of the Staphylococcus aureus NDK and the mutant enzymes. We also describe the crystal structures of the apo-NDK, as a transition state mimic with vanadate and in complex with different nucleotide substrates. These structures formed the basis for molecular dynamics simulations to understand the broad substrate specificity of this enzyme and the role of active site residues in the phospho-transfer mechanism and oligomerization. Put together, these data suggest that concerted changes in the conformation of specific residues facilitate the stabilization of nucleotide complexes thereby enabling the steps involved in the ping-pong reaction mechanism without large changes to the overall structure of this enzyme. | |||
Conformational basis for substrate recognition and regulation of catalytic activity in Staphylococcus aureus nucleoside di-phosphate kinase.,Srivastava SK, Rajasree K, Gopal B Biochim Biophys Acta. 2011 Jun 27. PMID:21745603<ref>PMID:21745603</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Nucleoside diphosphate kinase|Nucleoside diphosphate kinase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Nucleoside-diphosphate kinase]] | [[Category: Nucleoside-diphosphate kinase]] | ||
[[Category: Staphylococcus aureus subsp. aureus col]] | [[Category: Staphylococcus aureus subsp. aureus col]] | ||
[[Category: Gopal, B | [[Category: Gopal, B]] | ||
[[Category: Rajasree, K | [[Category: Rajasree, K]] | ||
[[Category: Srivastava, S K | [[Category: Srivastava, S K]] | ||
[[Category: Alpha-beta protein family]] | [[Category: Alpha-beta protein family]] | ||
[[Category: Ferridoxin fold]] | [[Category: Ferridoxin fold]] | ||
Revision as of 13:25, 19 December 2014
Crystal structure of Staphylococcus aureus nucleoside diphosphate kinaseCrystal structure of Staphylococcus aureus nucleoside diphosphate kinase
Structural highlights
Publication Abstract from PubMedNucleoside diphosphate kinases (NDK) are characterized by high catalytic turnover rates and diverse substrate specificity. These features make this enzyme an effective activator of a pro-drug-an application that has been actively pursued for a variety of therapeutic strategies. The catalytic mechanism of this enzyme is governed by a conserved histidine that coordinates a magnesium ion at the active site. Despite substantial structural and biochemical information on NDK, the mechanistic feature of the phospho-transfer that leads to auto-phosphorylation remains unclear. While the role of the histidine residue is well documented, the other active site residues, in particular the conserved serine remains poorly characterized. Studies on some homologues suggest no role for the serine residue at the active site, while others suggest a crucial role for this serine in the regulation and quaternary association of this enzyme in some species. Here we report the biochemical features of the Staphylococcus aureus NDK and the mutant enzymes. We also describe the crystal structures of the apo-NDK, as a transition state mimic with vanadate and in complex with different nucleotide substrates. These structures formed the basis for molecular dynamics simulations to understand the broad substrate specificity of this enzyme and the role of active site residues in the phospho-transfer mechanism and oligomerization. Put together, these data suggest that concerted changes in the conformation of specific residues facilitate the stabilization of nucleotide complexes thereby enabling the steps involved in the ping-pong reaction mechanism without large changes to the overall structure of this enzyme. Conformational basis for substrate recognition and regulation of catalytic activity in Staphylococcus aureus nucleoside di-phosphate kinase.,Srivastava SK, Rajasree K, Gopal B Biochim Biophys Acta. 2011 Jun 27. PMID:21745603[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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