8oqw: Difference between revisions
New page: '''Unreleased structure''' The entry 8oqw is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Crystal structure of Tannerella forsythia MurNAc kinase MurK== | |||
<StructureSection load='8oqw' size='340' side='right'caption='[[8oqw]], [[Resolution|resolution]] 2.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8oqw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Tannerella_forsythia Tannerella forsythia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OQW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OQW 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]] 2.05Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=8oqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oqw OCA], [https://pdbe.org/8oqw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oqw RCSB], [https://www.ebi.ac.uk/pdbsum/8oqw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oqw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/G8UQH9_TANFA G8UQH9_TANFA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The bacterial cell wall consists of a three-dimensional peptidoglycan layer, composed of peptides linked to the sugars N-acetylmuramic acid (MurNAc) and GlcNAc. Unlike other bacteria, the pathogenic Tannerella forsythia, a member of the red complex group of bacteria associated with the late stages of periodontitis, lacks biosynthetic pathways for MurNAc production and therefore obtains MurNAc from the environment. Sugar kinases play a crucial role in the MurNAc recycling process, activating the sugar molecules by phosphorylation. In this study, we present the first crystal structures of a MurNAc kinase, called murein sugar kinase (MurK), in its unbound state as well as in complexes with the ATP analogue beta-gamma-methylene adenosine triphosphate (AMP-PCP) and with MurNAc. We also determined the crystal structures of K1058, a paralogous MurNAc kinase of T. forsythia, in its unbound state and in complex with MurNAc. We identified the active site and residues crucial for MurNAc specificity as the less bulky side chains of S133, P134, and L135, which enlarge the binding cavity for the lactyl ether group, unlike the glutamate or histidine residues present in structural homologues. In establishing the apparent kinetic parameters for both enzymes, we showed a comparable affinity for MurNAc (K(m) 180 muM and 30 muM for MurK and K1058, respectively), with MurK being over two hundred times faster than K1058 (V(max) 80 and 0.34 mumol min(-1) mg(-1), respectively). These data might support a structure-guided approach to development of inhibitory MurNAc analogues for pathogen MurK enzymes. | |||
N-acetylmuramic acid recognition by MurK kinase from the MurNAc auxotrophic oral pathogen Tannerella forsythia.,Stasiak AC, Gogler K, Borisova M, Fink P, Mayer C, Stehle T, Zocher G J Biol Chem. 2023 Jul 20:105076. doi: 10.1016/j.jbc.2023.105076. PMID:37481208<ref>PMID:37481208</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8oqw" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Tannerella forsythia]] | |||
[[Category: Fink P]] | |||
[[Category: Gogler K]] | |||
[[Category: Stasiak AC]] | |||
[[Category: Stehle T]] | |||
[[Category: Zocher G]] | |||
Latest revision as of 13:40, 2 August 2023
Crystal structure of Tannerella forsythia MurNAc kinase MurKCrystal structure of Tannerella forsythia MurNAc kinase MurK
Structural highlights
FunctionPublication Abstract from PubMedThe bacterial cell wall consists of a three-dimensional peptidoglycan layer, composed of peptides linked to the sugars N-acetylmuramic acid (MurNAc) and GlcNAc. Unlike other bacteria, the pathogenic Tannerella forsythia, a member of the red complex group of bacteria associated with the late stages of periodontitis, lacks biosynthetic pathways for MurNAc production and therefore obtains MurNAc from the environment. Sugar kinases play a crucial role in the MurNAc recycling process, activating the sugar molecules by phosphorylation. In this study, we present the first crystal structures of a MurNAc kinase, called murein sugar kinase (MurK), in its unbound state as well as in complexes with the ATP analogue beta-gamma-methylene adenosine triphosphate (AMP-PCP) and with MurNAc. We also determined the crystal structures of K1058, a paralogous MurNAc kinase of T. forsythia, in its unbound state and in complex with MurNAc. We identified the active site and residues crucial for MurNAc specificity as the less bulky side chains of S133, P134, and L135, which enlarge the binding cavity for the lactyl ether group, unlike the glutamate or histidine residues present in structural homologues. In establishing the apparent kinetic parameters for both enzymes, we showed a comparable affinity for MurNAc (K(m) 180 muM and 30 muM for MurK and K1058, respectively), with MurK being over two hundred times faster than K1058 (V(max) 80 and 0.34 mumol min(-1) mg(-1), respectively). These data might support a structure-guided approach to development of inhibitory MurNAc analogues for pathogen MurK enzymes. N-acetylmuramic acid recognition by MurK kinase from the MurNAc auxotrophic oral pathogen Tannerella forsythia.,Stasiak AC, Gogler K, Borisova M, Fink P, Mayer C, Stehle T, Zocher G J Biol Chem. 2023 Jul 20:105076. doi: 10.1016/j.jbc.2023.105076. PMID:37481208[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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