5us3 | pdb_00005us3

Heterogeneous-backbone Foldamer Mimic of the Sp1-3 Zinc Finger

spinqualitylabelsall models 5us3 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5us3 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: B3D, B3K, B3Q, MAA, MMO, NH2, NLE, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed A variety of oligomeric backbones with compositions deviating from biomacromolecules can fold in defined ways. Termed "foldamers," these agents have diverse potential applications. A number of protein-inspired secondary structures (e.g., helices, sheets) have been produced from unnatural backbones, yet examples of tertiary folds combining several secondary structural elements in a single entity are rare. One promising strategy to address this challenge is the systematic backbone alteration of natural protein sequences, through which a subset of the native side chains is displayed on an unnatural building block to generate a heterogeneous backbone. A drawback to this approach is that substitution at more than one or two sites often comes at a significant energetic cost to fold stability. Here we report heterogeneous-backbone foldamers that mimic the zinc finger domain, a ubiquitous and biologically important metal-binding tertiary motif, and do so with a folded stability that is superior to the natural protein on which their design is based. A combination of UV-vis spectroscopy, isothermal titration calorimetry, and multidimensional NMR reveals that suitably designed oligomers with >20% modified backbones can form native-like tertiary folds with metal-binding environments identical to the prototype sequence (the third finger of specificity factor 1) and enhanced thermodynamic stability. These results expand the scope of heterogeneous-backbone foldamer design to a new tertiary structure class and show that judiciously applied backbone modification can be accompanied by improvement to fold stability. Heterogeneous-Backbone Foldamer Mimics of Zinc Finger Tertiary Structure.,George KL, Horne WS J Am Chem Soc. 2017 Jun 14;139(23):7931-7938. doi: 10.1021/jacs.7b03114. Epub, 2017 Jun 5. PMID:28509549 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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