Peptidyl amidating enzyme
Cone snails, genus Conus, are predatory marine snails that use venom to capture their prey.
This venom contains a diverse array of peptide toxins, known as conotoxins, which undergo a diverse set of posttranslational modifications.
The role of the propeptide has not been elucidated except in the case of gamma-carboxylation in which it has been shown to enhance the efficiency of carboxylation (Bandyopadhyay et al.,1998).
While the enzymes involved in proteolytic processing, disulfide bond formation, gamma-carboxylation of glutamate (Bandyopadhyay et al., 2002; Czerwiec et al., 2002), isomerization of proline has been characterized in conus venom duct the enzymes for the rather infrequent modifications, bromination of tryptophan and epimerization of amino acids remain to be identified.
One of the most common types of posttranslational modification many conotoxins undergo is C-terminal amidation. Conceptual translation product of c DNA encoding conotoxins and the sequences of the corresponding mature conotoxins containing posttranslational modifications in addition to amidation.
(γ = gamma-carboxy glutamate; The posttranslational modification of the C-terminus into an amide is catalyzed by the amidating, copper requiring enzyme peptidylglycine α-amidating monooxygenase (PAM). The first function, peptidyl α-hydroxylating monooxygenase (PHM) hydroxylates glycine at the C-terminal end of a given peptide (Eipper et al., 1992; Prigge et al., 2000).
Attenborough et al., suggest that bifunctional PAMs predate the evolution of the nervous and endocrine systems and the ancestral function may have been to amidate epitheliopeptides. Step I: PHM function hydroxylates glycine in the presence of oxygen, copper and ascorbate.
Using specific oligonucleotide primers and reverse transcription-polymerase chain reaction we have identified and cloned from the venom duct c DNA library, a c DNA with 49% homology to PAM from ) comprise ~700 species of venomous predatory mollusks (Olivera, 2006).
Reduction in the levels of Slpi which inhibits elastase, cathepsin G, trypsin and chymotrypsin is likely to alter the processing of proteins and peptides in the cells (Yin et al., 2011).
PAM is localized in the -golgi network and secretory vesicles in which the neuropeptides are processed (Mair et al., 2004; Milgram et al., 1997; Oyarce and Eipper, 2000).
Neuropeptides (RYIRF-NH2, GYIRF-NH2, and YIRF-NH2) that are potentially excitatory in schistosome muscles identified in flat-worms require the C-terminal amidated phenylalanine for activity (Day et al., 1994, 1997).
Inactivation of the PAM gene is lethal in homolog of cytochrome B561, a transmembrane protein present in synaptic vesicles and large dense core vesicles.