View source for 9qdp


==De novo designed enzyme for Morita-Baylis-Hillman reaction MBH2==
<StructureSection load='9qdp' size='340' side='right'caption='[[9qdp]], [[Resolution|resolution]] 1.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qdp]] is a 1 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=9QDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QDP 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]] 1.17&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=9qdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qdp OCA], [https://pdbe.org/9qdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qdp RCSB], [https://www.ebi.ac.uk/pdbsum/9qdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qdp ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Enzymes find broad use as biocatalysts in industry and medicine owing to their exquisite selectivity, efficiency and mild reaction conditions. Custom-designed enzymes can produce tailor-made biocatalysts with potential applications that extend beyond natural reactions. However, current design methods require testing a large number of designs and mostly produce de novo enzymes with low catalytic activities(1-3). As a result, they require costly experimental optimization and high-throughput screening to be industrially viable(4,5). Here we present rotamer inverted fragment finder-diffusion (Riff-Diff), a hybrid machine learning and atomistic modelling strategy for scaffolding catalytic arrays in de novo proteins. We highlight the general applicability of Riff-Diff by designing enzymes for two mechanistically distinct chemical transformations, the retro-aldol reaction and the Morita-Baylis-Hillman reaction. We show that in both cases, it is possible to generate catalysts that exhibit activities rivalling those optimized by in vitro evolution, along with exquisite stereoselectivity. High-resolution structures of six of the designs revealed near-atomic active site design precision. The design strategy can, in principle, be applied to any catalytically competent amino acid array. These findings lay the basis for practical applicability of de novo protein catalysts in synthesis and describe fundamental principles of protein design and enzyme catalysis.

Computational enzyme design by catalytic motif scaffolding.,Braun M, Tripp A, Chakatok M, Kaltenbrunner S, Fischer C, Stoll D, Bijelic A, Elaily W, Totaro MG, Moser M, Hoch SY, Lechner H, Rossi F, Aleotti M, Hall M, Oberdorfer G Nature. 2025 Dec 3. doi: 10.1038/s41586-025-09747-9. PMID:41339546<ref>PMID:41339546</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qdp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Fischer C]]
[[Category: Kaltenbrunner S]]
[[Category: Oberdorfer G]]
[[Category: Stoll D]]
[[Category: Tripp A]]