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Publication Abstract from PubMed

beta-Amino acids have a backbone that is expanded by one carbon atom relative to alpha-amino acids, and beta residues have been investigated as subunits in protein-like molecules that adopt discrete and predictable conformations. Two classes of beta residue have been widely explored in the context of generating alpha-helix-like conformations: beta(3) -amino acids, which are homologous to alpha-amino acids and bear a side chain on the backbone carbon adjacent to nitrogen, and residues constrained by a five-membered ring, such the one derived from trans-2-aminocyclopentanecarboxylic acid (ACPC). Substitution of alpha residues with their beta(3) homologues within an alpha-helix-forming sequence generally causes a decrease in conformational stability. Use of a ring-constrained beta residue, however, can offset the destabilizing effect of alpha-->beta substitution. Here we extend the study of alpha-->beta substitutions, involving both beta(3) and ACPC residues, to short loops within a small tertiary motif. We start from previously reported variants of the Pin1 WW domain that contain a two-, three-, or four-residue beta-hairpin loop, and we evaluate alpha-->beta replacements at each loop position for each variant. By referral to the varphi,psi angles of the native structure, one can choose a stereochemically appropriate ACPC residue. Use of such logically chosen ACPC residues enhances conformational stability in several cases. Crystal structures of three beta-containing Pin1 WW domain variants show that a native-like tertiary structure is maintained in each case.

Evaluation of beta-Amino Acid Replacements in Protein Loops: Effects on Conformational Stability and Structure.,Mortenson DE, Kreitler DF, Thomas NC, Guzei IA, Gellman SH, Forest KT Chembiochem. 2017 Dec 22. doi: 10.1002/cbic.201700580. PMID:29272560^[4]

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