View source for 7ldu


==Zoogloea ramigera biosynthetic thiolase Q183Y/Y218E/delH221 mutant==
<StructureSection load='7ldu' size='340' side='right'caption='[[7ldu]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ldu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Zoogloea_ramigera Zoogloea ramigera]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LDU 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]] 2.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=SCY:S-ACETYL-CYSTEINE'>SCY</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=7ldu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ldu OCA], [https://pdbe.org/7ldu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ldu RCSB], [https://www.ebi.ac.uk/pdbsum/7ldu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ldu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/THIL_SHIZO THIL_SHIZO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Activation of enzymes by monovalent cations (M+) is a widespread phenomenon in biology. Despite this, there are few structure-based studies describing the underlying molecular details. Thiolases are a ubiquitous and highly conserved family of enzymes containing both K+-activated and K+-independent members. Guided by structures of naturally occurring K+-activated thiolases, we have used a structure-based approach to engineer K+-activation into a K+-independent thiolase. To our knowledge, this is the first demonstration of engineering K+-activation into an enzyme, showing the malleability of proteins to accommodate M+ ions as allosteric regulators. We show that a few protein structural features encode K+-activation in this class of enzyme. Specifically, two residues near the substrate-binding site are sufficient for K+-activation: A tyrosine residue is required to complete the K+ coordination sphere, and a glutamate residue provides a compensating charge for the bound K+ ion. Further to these, a distal residue is important for positioning a K+-coordinating water molecule that forms a direct hydrogen bond to the substrate. The stability of a cation-pi interaction between a positively charged residue and the substrate is determined by the conformation of the loop surrounding the substrate-binding site. Our results suggest that this cation-pi interaction effectively overrides K+-activation, and is, therefore, destabilised in K+-activated thiolases. Evolutionary conservation of these amino acids provides a promising signature sequence for predicting K+-activation in thiolases. Together, our structural, biochemical and bioinformatic work provide important mechanistic insights into how enzymes can be allosterically activated by M+ ions.

Engineering potassium activation into biosynthetic thiolase.,Marshall AC, Bruning JB Biochem J. 2021 Aug 13;478(15):3047-3062. doi: 10.1042/BCJ20210455. PMID:34338286<ref>PMID:34338286</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ldu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thiolase 3D structures|Thiolase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Zoogloea ramigera]]
[[Category: Bruning JB]]
[[Category: Marshall AC]]