9ym7

Backbone Modification in the Villin Headpiece Miniprotein: HP35 with Calpha-methyl-Phe at Positions 6 and 17, ACPC at Position 29

spinqualitylabelsall models 9ym7 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ym7 is a 1 chain structure with sequence from Gallus gallus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, models Ligands: A1APM, NH2, NLE, XCP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Changing the backbone connectivity of proteins can impart useful new traits while maintaining essential structural and functional features. In design of artificial proteomimetic agents, backbone modification is usually isolated to sites that are solvent-exposed in the folded state, as similar changes at buried residues can alter the fold. Recent work has shown that core backbone modification without structural perturbation is possible; however, the modifications in that study were consistently destabilizing and made in a prototype of exceptionally high conformational stability. Here, we report efforts to broaden the scope and improve the efficacy of core backbone engineering by applying it to the C-terminal subdomain of villin headpiece. A series of variants are prepared in which different artificial residue types are incorporated at core positions throughout the sequence, including a crucial aromatic triad. Impacts on folding energetics are quantified by biophysical methods, and high-resolution structures of several variants determined by NMR. We go on to construct a variant with approximately 40% of its core modified that adopts a fold identical to the prototype while showing enhanced thermodynamic stability. Backbone engineering in the hydrophobic core of villin headpiece.,Lin Y, David RM, Amin DM, Osborne SWJ, Horne WS RSC Chem Biol. 2025 Dec 17. doi: 10.1039/d5cb00269a. PMID:41450753 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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