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Showing results 1 to 6 of 6

Journal article

A Recombinant Approach For Stapled Peptide Discovery Yields Inhibitors of the RAD51 Recombinase

Authors : Pantelejevs, Teodors (2023)

Stapling is a macrocyclisation method that connects amino acid side chains of a peptide to improve its pharmacological properties. We describe an approach for stapled peptide preparation and biochemical evaluation that combines recombinant expression of fusion constructs of target peptides and cysteine-reactive divinylheteroaryl chemistry, as an alternative to solid-phase synthesis. We then employ this workflow to prepare and evaluate BRC-repeatderived ...

Journal article

Discovery of diverse human BH3-only and non-native peptide binders of pro-apoptotic BAK indicate that activators and inhibitors use a similar binding mode and are not distinguished by binding affinity or kinetics

Authors : Aguilar, Fiona (2023)

Apoptosis is a programmed form of cell death important for the development and maintenance of tissue homeostasis. The BCL-2 protein family controls key steps in apoptosis, dysregulation of which can lead to a wide range of human diseases. BCL-2 proteins comprise three groups: anti-apoptotic proteins, proapoptotic proteins, and BH3-only proteins. BAK is one of two pro-apoptotic proteins, and previous work has shown that binding of certain&#x...

Journal Article

Evolutionary spread of protein L-(iso)aspartyl O-methyltransferases guides the discovery of distinct isoaspartate-containing peptides, pimtides

Authors : Lee, Hyunbin (2023)

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse class of natural products with a distinct biosynthetic logic, the enzymatic modification of genetically encoded precursor peptides. Although their structural and biosynthetic diversity remains largely underexplored, the identification of novel subclasses with unique structural motifs and biosynthetic pathways has been challenging. Here, we report that protein L-(iso)aspartyl O-methyltransferases&#x...

Journal article

Influence of the TorD signal peptide chaperone on Tat-dependent protein translocation

Authors : Bageshwar, Umesh K. (2021)

The twin-arginine translocation (Tat) pathway transports folded proteins across energetic membranes. Numerous Tat substrates contain co-factors that are inserted before transport with the assistance of redox enzyme maturation proteins (REMPs), which bind to the signal peptide of precursor proteins. How signal peptides are transferred from a REMP to a binding site on the Tat receptor complex remains unknown. Since the signal peptide mediates both ...

Journal article

Molecular determinants of TRAF6 binding specificity suggest that native interaction partners are not optimized for affinity

Authors : Halpin, Jackson C. (2023)

TRAF6 is an adapter protein and E3 ubiquitin ligase involved in signaling downstream of cell receptors essential for development and the immune system. TRAF6 participates in many protein-protein interactions, some of which are mediated by a C-terminal MATH domain that recruits TRAF6 to cell-surface receptors and associated proteins. The TRAF6 MATH domain binds to short peptide segments containing the motif PxExx[FYWHDE], where x is any amino acid. Blocki...

Journal article

Structural characterization of the antimicrobial peptides myxinidin and WMR in bacterial membrane mimetic micelles and bicelles

Authors : Cherniavskyi, Yevhen K. (2021)

Antimicrobial peptides are a promising class of alternative antibiotics that interact selectively with negatively charged lipid bilayers. This paper presents the structural characterization of the antimicrobial peptides myxinidin and WMR associated with bacterial membrane mimetic micelles and bicelles by NMR, CD spectroscopy, and Molecular Dynamics simulations. Both peptides adopt a different conformation in the lipidic environment than in aqueous solution. The...