View source for 6yrs


==Structure of a new variant of GNCA ancestral beta-lactamase==
<StructureSection load='6yrs' size='340' side='right'caption='[[6yrs]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6yrs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YRS 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=6yrs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yrs OCA], [https://pdbe.org/6yrs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yrs RCSB], [https://www.ebi.ac.uk/pdbsum/6yrs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yrs ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
TEM-1 beta-lactamase degrades beta-lactam antibiotics with a strong preference for penicillins. Sequence reconstruction studies indicate that it evolved from ancestral enzymes that degraded a variety of beta-lactam antibiotics with moderate efficiency. This generalist to specialist conversion involved more than 100 mutational changes, but conserved fold and catalytic residues, suggesting a role for dynamics in enzyme evolution. Here, we develop a conformational dynamics computational approach to rationally mold a protein flexibility profile on the basis of a hinge-shift mechanism. By deliberately weighting and altering the conformational dynamics of a putative Precambrian beta-lactamase, we engineer enzyme specificity that mimics the modern TEM-1 beta-lactamase with only 21 amino acid replacements. Our conformational dynamics design thus re-enacts the evolutionary process and provides a rational allosteric approach for manipulating function while conserving the enzyme active site.

Hinge-shift mechanism as a protein design principle for the evolution of beta-lactamases from substrate promiscuity to specificity.,Modi T, Risso VA, Martinez-Rodriguez S, Gavira JA, Mebrat MD, Van Horn WD, Sanchez-Ruiz JM, Banu Ozkan S Nat Commun. 2021 Mar 25;12(1):1852. doi: 10.1038/s41467-021-22089-0. PMID:33767175<ref>PMID:33767175</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6yrs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Gavira JA]]
[[Category: Martinez-Rodriguez S]]
[[Category: Modi T]]
[[Category: Ozkan SB]]
[[Category: Risso V]]
[[Category: Sanchez-Ruiz JM]]