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Publication Abstract from PubMed

<div class="abstract"> <div><p class="Abstract" style="margin: 0in 0in 0.25in; text-align: justify; line-height: 11.25pt; font-size: 8pt; font-family: Arial, sans-serif; caret-color: rgb(0, 0, 0); color: rgb(0, 0, 0);">To mimic a hypothetical pathway for protein evolution, we previously developed a design strategy (Metal-Templated Interface Redesign), in which a monomeric protein (cytochrome&nbsp;<i>cb₅</i><sub>62&l t;/sub>) was tailored for metal-mediated self-assembly, followed by the re-design of the resulting oligomers for enhanced stability and metal-based functions. Here we show that a single hydrophobic mutation on the cytochrome&nbsp;<i>cb</i>₅₆₂&nbsp;surf ace can drastically alter the outcome of metal-directed oligomerization to yield a new trimeric architecture, (TriCyt1)₃, featuring an unusual hexa-histidine coordination motif. Through computational and rational redesign, this nascent trimer is converted into second and third-generation variants (TriCyt2)₃&nbsp;and (TriCyt3)₃&nbsp;with increased structural stability and preorganization for metal coordination. The three TriCyt variants combined furnish a unique design platform to a) provide tunable coupling between protein quaternary structure and metal coordination, b) enable the construction of metal/pH-switchable protein oligomerization motifs, and c) generate a robust metal coordination site that can accommodate all mid-to-late first-row transition metal ions with high affinity, including Mn(II) with nanomolar dissociation constants,&nbsp;&nbsp;rivaling those of the strongest Mn(II)-binding protein, calprotectin.&nbsp;<span lang="EN-GB" style="color: red;"><o:p></o:p></span></p> </div> </div>.

Metal-Templated Design of Chemically Switchable Protein Assemblies with High-Affinity Coordination Sites.,Tezcan FA, Kakkis A, Gagnon D, Esselborn J, Britt RD Angew Chem Int Ed Engl. 2020 Aug 23. doi: 10.1002/anie.202009226. PMID:32830423^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.