6u1e: Difference between revisions
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<StructureSection load='6u1e' size='340' side='right'caption='[[6u1e]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='6u1e' size='340' side='right'caption='[[6u1e]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6u1e]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6u1e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U1E FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RB:RUBIDIUM+ION'>RB</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RB:RUBIDIUM+ION'>RB</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=6u1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u1e OCA], [https://pdbe.org/6u1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u1e RCSB], [https://www.ebi.ac.uk/pdbsum/6u1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u1e ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DDL_THET8 DDL_THET8] Cell wall formation.[HAMAP-Rule:MF_00047] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6u1e" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6u1e" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[D-alanine-D-alanine ligase 3D structures|D-alanine-D-alanine ligase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Thermus thermophilus HB8]] | ||
[[Category: Bruning | [[Category: Bruning JB]] | ||
[[Category: Pederick | [[Category: Pederick JL]] | ||
Latest revision as of 10:42, 11 October 2023
Thermus thermophilus D-alanine-D-alanine ligase in complex with ATP, D-alanine-D-alanine, Mg2+ and Rb+Thermus thermophilus D-alanine-D-alanine ligase in complex with ATP, D-alanine-D-alanine, Mg2+ and Rb+
Structural highlights
FunctionDDL_THET8 Cell wall formation.[HAMAP-Rule:MF_00047] Publication Abstract from PubMedThe ATP-grasp superfamily of enzymes shares an atypical nucleotide-binding site known as the ATP-grasp fold. These enzymes are involved in many biological pathways in all domains of life. One ATP-grasp enzyme, D-alanine-D-alanine ligase (Ddl), catalyzes the ATP-dependent formation of the D-alanyl-D-alanine dipeptide essential for bacterial cell-wall biosynthesis, and is therefore an important antibiotic drug target. Ddl is activated by the monovalent cation (MVC) K(+), but despite its clinical relevance and decades of research, how this activation occurs has not been elucidated. We demonstrate here that activating MVCs bind adjacent to the active site of Ddl from Thermus thermophilus and used a combined biochemical and structural approach to characterize the MVC activation. We found that TtDdl is a Type II MVC-activated enzyme, retaining activity in the absence of MVCs. However, the efficiency of TtDdl increased ~20-fold in the presence of activating MVCs, and it was maximally activated by K(+) and Rb(+) ions. A strict dependence on ionic radius of the MVC was observed, with Li(+) and Na(+) providing little-to-no TtDdl activation. To understand the mechanism of MVC activation, we solved crystal structures of TtDdl representing distinct catalytic stages in complex with K(+), Rb(+), or Cs(+) Comparison of these structures with apo TtDdl revealed no evident conformational change on MVC binding. Of note, the identified MVC-binding site is structurally conserved within the ATP-grasp superfamily. We propose that MVCs activate Ddl by altering the charge distribution of its active site. These findings provide insight into the catalytic mechanism of ATP-grasp enzymes. D-alanine-D-alanine ligase as a model for the activation of ATP-grasp enzymes by monovalent cations.,Pederick JL, Thompson AP, Bell SG, Bruning JB J Biol Chem. 2020 Apr 25. pii: RA120.012936. doi: 10.1074/jbc.RA120.012936. PMID:32335509[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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