View source for 9qup


==Tb(III)-bound de novo protein scaffold TFD-EE MPNN==
<StructureSection load='9qup' size='340' side='right'caption='[[9qup]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qup]] 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=9QUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QUP 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TB:TERBIUM(III)+ION'>TB</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=9qup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qup OCA], [https://pdbe.org/9qup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qup RCSB], [https://www.ebi.ac.uk/pdbsum/9qup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qup 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qup" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Badmann T]]
[[Category: Delhommel F]]
[[Category: Groll M]]
[[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]]