View source for 8qzk


==Catalytic core of endo-alpha-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) concieved by deep network hallucination: dEngBF4 Hexagonal form==
<StructureSection load='8qzk' size='340' side='right'caption='[[8qzk]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qzk]] 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=8QZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QZK 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]] 3.25&#8491;</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=8qzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qzk OCA], [https://pdbe.org/8qzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qzk RCSB], [https://www.ebi.ac.uk/pdbsum/8qzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qzk ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Enzymes are indispensable biocatalysts for numerous industrial applications, yet stability, selectivity, and restricted substrate recognition present limitations for their use. Despite the importance of enzyme engineering in overcoming these limitations, success is often challenged by the intricate architecture of enzymes derived from natural sources. Recent advances in computational methods have enabled the de novo design of simplified scaffolds with specific functional sites. Such scaffolds may be advantageous as platforms for enzyme engineering. Here, we present a strategy for the de novo design of a simplified scaffold of an endo-alpha-N-acetylgalactosaminidase active site, a glycoside hydrolase from the GH101 enzyme family. Using a combination of trRosetta hallucination, iterative cycles of deep-learning-based structure prediction, and ProteinMPNN sequence design, we designed proteins with 290 amino acids incorporating the active site while reducing the molecular weight by over 100 kDa compared to the initial endo-alpha-N-acetylgalactosaminidase. Of 11 tested designs, six were expressed as soluble monomers, displaying similar or increased thermostabilities compared to the natural enzyme. Despite lacking detectable enzymatic activity, the experimentally determined crystal structures of a representative design closely matched the design with a root-mean-square deviation of 1.0 A, with most catalytically important side chains within 2.0 A. The results highlight the potential of scaffold hallucination in designing proteins that may serve as a foundation for subsequent enzyme engineering.

Carving out a Glycoside Hydrolase Active Site for Incorporation into a New Protein Scaffold Using Deep Network Hallucination.,Hansen AL, Theisen FF, Crehuet R, Marcos E, Aghajari N, Willemoes M ACS Synth Biol. 2024 Mar 15;13(3):862-875. doi: 10.1021/acssynbio.3c00674. Epub , 2024 Feb 15. PMID:38357862<ref>PMID:38357862</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8qzk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Aghajari N]]
[[Category: Crehuet R]]
[[Category: Hansen AL]]
[[Category: Marcos E]]
[[Category: Thiesen FF]]
[[Category: Willemoes M]]