Mammalian l-to- d-amino-acid-residue isomerase from platypus venom

• Published in: FEBS letters 2006-03, Vol.580 (6), p.1587-1591
• Main Authors: Torres, Allan M., Tsampazi, Maria, Tsampazi, Chryssanthi, Kennett, Eleanor C., Belov, Katherine, Geraghty, Dominic P., Bansal, Paramjit S., Alewood, Paul F., Kuchel, Philip W.
• Format: Article
• Language: English
• Subjects: Amino Acid Isomerases - antagonists & inhibitors; Amino Acid Isomerases - chemistry; Amino Acid Isomerases - isolation & purification; Amino Acid Sequence; Animals; defensin-like peptide; DLP; Methanol - pharmacology; Molecular Sequence Data; molecular weight; Ornithorhyncus venom C-type natriuretic peptide; OvCNP; Peptide isomerase; Peptides - pharmacology; Platypus - metabolism; Platypus venom peptide; reverse-phase HPLC; RP-HPLC; Venoms - enzymology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.01.089

The presence of d-amino-acid-containing polypeptides, defensin-like peptide (DLP)-2 and Ornithorhyncus venom C-type natriuretic peptide (OvCNP)b, in platypus venom suggested the existence of a mammalian d-amino-acid-residue isomerase(s) responsible for the modification of the all- l-amino acid precursors. We show here that this enzyme(s) is present in the venom gland extract and is responsible for the creation of DLP-2 from DLP-4 and OvCNPb from OvCNPa. The isomerisation reaction is freely reversible and under well defined laboratory conditions catalyses the interconversion of the DLPs to full equilibration. The isomerase is ∼50–60 kDa and is inhibited by methanol and the peptidase inhibitor amastatin. This is the first known l-to- d-amino-acid-residue isomerase in a mammal.