Crystal structures of peptide enantiomers and racemates: Probing conformational diversity in heterochiral Pro‐Pro sequences

Abstract

Background: Heart disease is the leading cause of tobacco‐related death in smokers and of deaths due to secondhand smoke (SHS) exposure in nonsmokers. This study centers on the development and evaluation of an evidence‐based model curriculum for improving clinical attention to tobacco use and SHS exposure in cardiology. Hypothesis: We hypothesized that the curriculum would be associated with improvements in clinician tobacco‐related knowledge, attitudes, confidence, and counseling behaviors from pre‐to post‐training and at the 3‐month follow‐up. Methods: The 1‐hour Cardiology Rx for Change curriculum was evaluated with 22 cardiology fellows and 77 medical residents with consistent training effects observed between the 2 groups. Results: Trainees' tobacco treatment knowledge increased significantly from pre‐ to post‐training (t[81] = 6.51, P<0.001), and perceived barriers to providing cessation treatment decreased significantly (t[81] = −3.97, P<0.001). The changes, however, were not sustained at the 3‐month follow‐up, suggesting the need for booster training efforts. From pretraining to 3‐month follow‐up, the training was associated with significant sustained gains in clinician confidence for treating tobacco dependence (t[61] = 3.69, P = 0.001) and with improvements in clinicians assessing patients' readiness to quit smoking (from 61% to 79%, t[59] = 3.69,P<0.001) and providing assistance with quitting (from 47% to 59%, t[59] = 2.12, P = 0.038). Asking patients about tobacco use, advising cessation, and arranging follow‐up also increased over time, but not significantly. All participants (100%) recommended the curriculum for dissemination to other training programs. Conclusions: Available online via http://rxforchange.ucsf.edu, Cardiology Rx for Change offers a packaged training tool for improving treatment of tobacco use and SHS exposure in cardiology care. © 2011 Wiley Periodicals, Inc. This work was supported by the Flight Attendant Medical Research Institute (FAMRI) William Cahan Distinguished Professor Award (PI: W. Grossman), and the State of California Tobacco‐Related Disease Research Program (# 17RT‐0077, PI: J.J. Prochaska). The authors have no other funding, financial relationships, or conflicts of interest to disclose.

The nucleotide addition cycle of RNA polymerase is controlled by two molecular hinges in the Bridge Helix domain

“…The activity of the Q823-P/S824-P double mutant proves explicitly that the presence of two proline residues in this particular location of the Bridge Helix is not only compatible with catalytic function, but also compatible with superactivity. Prolyl-proline preferentially adopt an elongated polyproline II structure (87%), or less frequently (13%) a β-turn (Additional file 4A; [43,44]). Either of the structures would cause a substantial local increase in the flexibility of BH-H C .…”

Investigating diproline segments in proteins: Occurrences, conformation and classification

“…48 The occurrence of cis peptide bonds in proteins involving proline is a noteworthy feature in proteins. [49][50][51] The allowed regions of /, w space for both L-and D-proline residues has been investigated in an earlier study, 5,6 using designed peptides containing homochiral and heterochiral diproline segments. In the current analysis, the possible conformational states for the diproline segment ( L Pro-L Pro) found in proteins taken from a non-redundant dataset has been investigated and identified with an emphasis on the cis and trans states for the peptide bond between the diproline segment.…”

“…The direct consequence of the pyrrolidine ring formation restricts the torsional angle / to values of 2608 AE 308 for the L-proline residue which has been clearly exploited in the design of well structured peptides. [1][2][3][4][5][6] Generally, proline exists in the following three stable conformations: (i) polyproline (P II ) region (/ $ 2608, w $ 1208), (ii) the C 7 region or c-turn (/ $ 2708, w $ 708), and (iii) right handed a helical region a R (/ $ 2608, w $ 2308). It is now well established that the presence of L-proline in proteins has a large effect on their conformation.…”

Conformationally Constrained Peptides from CD2 To Modulate Protein–Protein Interactions between CD2 and CD58

“…The β-turn was stabilized by an intramolecular hydrogen bond between Ile9 C=O and Ile2 NH. Overall, the structure resembled a β-hairpin structure with D-Pro-Pro stabilizing and nucleating the hairpin structure 24 .…”