Crystal state conformation of three model monomer units for the β-bend ribbon structure

The molecular and crystal structures of three compounds, representing the repeating units of the β-bend ribbon (an approximate 310-helix, with an intramolecular hydrogen-bonding donor every two residues), have been determined by x-ray diffraction. They are Boc-Aib-Hib-NHBzl, Z-Aib-Hib-NHBzl, and Z-L-Hyp-Aib-NHMe (Aib, α-aminoisobutyric acid; Bzl, benzyl; Boc, t-butyloxycarbonyl; Hyp, hydroxyproline Hib, α-hydroxyisobutyric acid; Z, benzyloxycarbonyl). The two former compounds are folded in a -bend conformation: type III (III′) for Boc-Aib-Hib-NHBzl, while type II (II′) for the Z analogue. Conversely, the structure of Z-L-Hyp-Aib-NHMe, although not far from a type II β-bend, is partially open

Peptides from chiral Calpha,alpha-disubstituted glycines : crystallographic characterization of conformation of Calpha-methyl, Calpha-isopropylglycine [(alphaMe)Val] in simple derivatives and model peptides

The mol. and crystal structures of R-L-(aMe)Val-R1 [R = ClCH2CO, R1 = OH; R = Z, R1 = Ala-Ala-OMe (I); R = Ac-Aib-Aib, Z-Aib, R1 = Aib-Aib-OCMe3; (aMe)Val = NHCMe(CHMe2)CO; Z = PhCH2O2C; Aib = NHCMe2CO] were detd. by x-ray diffraction. Tripeptide I adopts a type-I b-turn conformation stabilized by a

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

We review work on the paramagnetic amino acid 2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid, TOAC, and its applications in studies of peptides and peptide synthesis. TOAC was the first spin label probe incorporated in peptides by means of a peptide bond. In view of the rigid character of this cyclic molecule and its attachment to the peptide backbone via a peptide bond, TOAC incorporation has been very useful to analyze backbone dynamics and peptide secondary structure. Many of these studies were performed making use of EPR spectroscopy, but other physical techniques, such as X-ray crystallography, CD, fluorescence, NMR, and FT-IR, have been employed. The use of double-labeled synthetic peptides has allowed the investigation of their secondary structure. A large number of studies have focused on the interaction of peptides, both synthetic and biologically active, with membranes. In the latter case, work has been reported on ligands and fragments of GPCR, host defense peptides, phospholamban, and β-amyloid. EPR studies of macroscopically aligned samples have provided information on the orientation of peptides in membranes. More recent studies have focused on peptide–protein and peptide–nucleic acid interactions. Moreover, TOAC has been shown to be a valuable probe for paramagnetic relaxation enhancement NMR studies of the interaction of labeled peptides with proteins. The growth of the number of TOAC-related publications suggests that this unnatural amino acid will find increasing applications in the future

Simulating the cross-linguistic pattern of Optional Infinitive errors in children’s declaratives and Wh- questions

One of the most striking features of children’s early multi-word speech is their tendency to produce non-finite verb forms in contexts in which a finite verb form is required (Optional Infinitive [OI] errors, Wexler, 1994). MOSAIC is a computational model of language learning that simulates developmental changes in the rate of OI errors across several different languages by learning compound finite constructions from the right edge of the utterance (Freudenthal, Pine, Aguado-Orea, & Gobet, 2007; Freudenthal, Pine, & Gobet, 2006a, 2009). However, MOSAIC currently only simulates the pattern of OI errors in declaratives, and there are important differences in the cross-linguistic patterning of OI errors in declaratives and Wh- questions. In the present study, we describe a new version of MOSAIC that learns from both the right and left edges of the utterance. Our simulations demonstrate that this new version of the model is able to capture the cross-linguistic patterning of OI errors in declaratives in English, Dutch, German and Spanish by learning from declarative input, and the cross-linguistic patterning of OI errors in Wh- questions in English, German and Spanish by learning from interrogative input. These results show that MOSAIC is able to provide an integrated account of the cross-linguistic patterning of OI errors in declaratives and Wh- questions, and provide further support for the view, instantiated in MOSAIC, that OI errors are compound-finite utterances with missing modals or auxiliaries

Identification of Coevolving Residues and Coevolution Potentials Emphasizing Structure, Bond Formation and Catalytic Coordination in Protein Evolution

The structure and function of a protein is dependent on coordinated interactions between its residues. The selective pressures associated with a mutation at one site should therefore depend on the amino acid identity of interacting sites. Mutual information has previously been applied to multiple sequence alignments as a means of detecting coevolutionary interactions. Here, we introduce a refinement of the mutual information method that: 1) removes a significant, non-coevolutionary bias and 2) accounts for heteroscedasticity. Using a large, non-overlapping database of protein alignments, we demonstrate that predicted coevolving residue-pairs tend to lie in close physical proximity. We introduce coevolution potentials as a novel measure of the propensity for the 20 amino acids to pair amongst predicted coevolutionary interactions. Ionic, hydrogen, and disulfide bond-forming pairs exhibited the highest potentials. Finally, we demonstrate that pairs of catalytic residues have a significantly increased likelihood to be identified as coevolving. These correlations to distinct protein features verify the accuracy of our algorithm and are consistent with a model of coevolution in which selective pressures towards preserving residue interactions act to shape the mutational landscape of a protein by restricting the set of admissible neutral mutations

X-ray Crystallographic Structure of an Artificial β-Sheet Dimer

This paper describes the X-ray crystallographic structure of a designed cyclic beta-sheet peptide that forms a well-defined hydrogen-bonded dimer that mimics beta-sheet dimers formed by proteins. The 54-membered ring macrocyclic peptide (1a) contains molecular template and turn units that induce beta-sheet structure in a heptapeptide strand that forms the dimerization interface. The X-ray crystallographic structure reveals the structures of the two "Hao" amino acids that help template the beta-sheet structure and the two delta-linked ornithine turn units that link the Hao-containing template to the heptapeptide beta-strand. The Hao amino acids adopt a conformation that resembles a tripeptide in a beta-strand conformation, with one edge of the Hao unit presenting an alternating array of hydrogen-bond donor and acceptor groups in the same pattern as that of a tripeptide beta-strand. The delta-linked ornithines adopt a conformation that resembles a hydrogen-bonded beta-turn, in which the ornithine takes the place of the i+1 and i+2 residues. The dimers formed by macrocyclic beta-sheet 1a resemble the dimers of many proteins, such as defensin HNP-3, the lambda-Cro repressor, interleukin 8, and the ribonuclease H domain of HIV-1 reverse transcriptase. The dimers of 1a self-assemble in the solid state into a barrel-shaped trimer of dimers in which the three dimers are arranged in a triangular fashion. Molecular modeling in which one of the three dimers is removed and the remaining two dimers are aligned face-to-face provides a model of the dimers of dimers of closely related macrocyclic beta-sheet peptides that were observed in solution

Conformationally controlled, thymine-based alpha-nucleopeptides

Rigid peptide backbones and backbone-to-side chain H-bonds permit the design of a-nucleopeptides with known 3D-structure; thymine–thymine base pairing is also observed