News from the group:
CAMDA'17 Conference
ISMB/ECCB Track
22-23 July 2017,
Prague, Czech Republic
(read more)
Outstanding Presentation Prize
for PP Łabaj
at CAMDA'15 (photo)
OeAW APART fellowship
for PP Łabaj
(photo)

Sequencing Quality Control (SEQC) project,
MAQC Consortium 2011–2014 (read more)
Host–parasite interactions in biocontrol, WWTF grant 2010–2013 (read more)

Power and limitations of RNA-Seq,
FDA SEQC, Nature Biotechnology (read more)
Characterization and improvement of RNA-Seq precision,
Bioinformatics (read more)
Impact of heavy tails in microarray analysis, Bioinformatics (read more)
Novel conserved repeats in sorting signals,
FEBS Journal (read more)
Sound sensation gene,
Nature communications
(read more)
RNA interference in ageing research,
Gerontology (read more)

A search for vertebrate peptides containing D-amino acids (FWF P22782)

In multicellular organisms many vital functions are mediated by peptides. Some of these peptides contain a D-amino acid in a well-defined position. To date, in all vertebrates and several invertebrates the D-amino acid is the second residue of the mature peptide whereas it has been found in other positions in invertebrates. Vertebrate peptides comprise dermorphins, deltorphins, and the peptide antibiotics bombinin H from frog skin, as well as a C-type natriuretic peptide (CNP) and beta-defensin-like peptide (DLP) from the venom of male Platypus, a primitive mammal. In case of the opioid peptides, the all L-forms are inactive, whereas subtle differences in activity and physicochemical properties between the two diastereomers of bombinin H have been observed. From skin secretions of Bombinae, an enzyme has been isolated which catalyses the posttranslational inversion of the stereochemistry of the respective L-amino acids present in the precursor of bombinin H. This L/D-isomerase acts exclusively on the second residue. Genes encoding polypeptides related to the frog skin enzyme are present in many vertebrates including man supporting the idea of the existence of diastereomeric peptides in higher mammals. A detailed study of the substrate specificity of the frog isomerase and subsequent data base search has led to the identification of potential substrates, which include hormones, antibacterial peptides etc., for which a D-form could exist as well. Based on this knowledge, we mainly focus on the questions, whether i) the diastereomeric form of a few selected peptides can be detected in animal tissues and thus the presence of the D-residue be directly confirmed, and ii) the biological activity and/or physicochemical properties of the peptides are modulated by the stereoinversion. In particular, the D-amino acid could crucially affect receptor interactions, folding propensities or polypeptide turnover in these pepides and thus have far-ranging consequences on their biological function.

Participants

Alexander Jilek - Projekt Leader

Farghaly Mohammed Farghaly Ali - Pre-Doctoral Fellow

Omair Rauf - Diploma Student

Rasha Ramadan Aly - Technical Assistant

Project-related publications

Gehmayr, V; Mollay, C; Reith, L; Müller, N; Jilek, A. Tight binding of transition-state analogues to a peptidyl-aminoacyl-L/D-isomerase from frog skin. Chembiochem. 2011;12:1996-2000;

Jilek, A; Mollay, C; Lohner, K; Kreil, G. Substrate specificity of a peptidyl-aminoacyl-L/D-isomerase from frog skin. Amino Acids. 2011 Mar 22.

Gössler-Schöfberger, R; Hesser, G; Muik, M; Wechselberger, C; Jilek, A. An orphan dermaseptin from frog skin reversibly assembles to amyloid-like aggregates in a pH-dependent fashion. FEBS J. 2009;276:5849-59.

Zangger, K; Gössler, R; Khatai, L; Lohner, K; Jilek, A. Structures of the glycine-rich diastereomeric peptides bombinin H2 and H4. Toxicon. 2008;52:246-54.

Jilek, A; Mollay, C; Tippelt, C; Grassi, J; Mignogna, G; Müllegger, J; Sander, V; Fehrer, C; Barra, D; Kreil, G. Biosynthesis of a D-amino acid in peptide linkage by an enzyme from frog skin secretions. Proc Natl Acad Sci U S A. 2005;102:4235-9.

Invited Reviews:

Jilek, A and Kreil, G. D-Amino Acids in Animal Peptides. 2008; 139:1-5.