9quc: Difference between revisions
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New page: '''Unreleased structure''' The entry 9quc is ON HOLD Authors: Wagner Egea, P., Delhommel, F., Mustafa, G., Leiss-Maier, F., Klimper, L., Badmann, T., Heider, A., Wille, I.C., Groll, M.,... |
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==Metal-free de novo protein scaffold TFD-EH== | |||
<StructureSection load='9quc' size='340' side='right'caption='[[9quc]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9quc]] 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=9QUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QUC 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]] 1.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=9quc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9quc OCA], [https://pdbe.org/9quc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9quc RCSB], [https://www.ebi.ac.uk/pdbsum/9quc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9quc ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Incorporating metal cofactors into computationally designed protein scaffolds provides a versatile route to novel protein functions, including the potential for new-to-nature enzyme catalysis. However, a major challenge in protein design is to understand how the scaffold architecture influences conformational dynamics. Here, we characterized structure and dynamics of a modular de novo scaffold with flexible inter-domain linkers. Three rationally engineered variants with different metal specificity were studied by combining X-ray crystallography, NMR spectroscopy, and molecular dynamics simulations. The lanthanide-binding variant was initially trapped in an inactive conformational state, which impaired efficient metal coordination and cerium-dependent photocatalytic activity. Stabilization of the active conformation by AI-guided sequence optimization using ProteinMPNN led to accelerated lanthanide binding and a 10-fold increase in k(cat)/K(m) for a photoenzymatic model reaction. Our results suggest that modular scaffold architectures provide an attractive starting point for de novo metalloenzyme engineering and that ProteinMPNN-based sequence redesign can stabilize desired conformational states. | |||
Modular protein scaffold architecture and AI-guided sequence optimization facilitate de novo metalloenzyme engineering.,Wagner Egea P, Delhommel F, Mustafa G, Leiss-Maier F, Klimper L, Badmann T, Heider A, Wille I, Groll M, Sattler M, Zeymer C Structure. 2025 Nov 5:S0969-2126(25)00397-1. doi: 10.1016/j.str.2025.10.010. PMID:41197620<ref>PMID:41197620</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9quc" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: | [[Category: Badmann T]] | ||
[[Category: | [[Category: Delhommel F]] | ||
[[Category: | [[Category: Groll M]] | ||
[[Category: | [[Category: Heider A]] | ||
[[Category: Klimper L]] | |||
[[Category: Leiss-Maier F]] | |||
[[Category: Mustafa G]] | |||
[[Category: Sattler M]] | |||
[[Category: Wagner Egea P]] | |||
[[Category: Wille IC]] | |||
[[Category: Zeymer C]] | |||
