Dibasic convertase

Metalloendo-peptidases (Nardilysin, N-Arginine Dibasic Convertase)... 

The metalloendopeptidase nardilysin (N-arginine dibasic convertase NRDc) enhances a-cleavage of APP, which results in the decreased generation of Ap in vitro. The neuron-specific overexpression of NRDc prevents Ap deposition in the AD mouse model. The activity of a-secretase in the mouse brain was enhanced by the overexpression of NRDc, and was reduced by the deletion of NRDc. NRDc controls Ap formation through the regulation of a-secretase [428],... 

The growing family of known divalent cation-dependent proteases such as insulinase [51] and dibasic convertase [52], with the variant consensus HxxeH, also present interesting questions as to the possibility of a mirrored active site with or without conservation of the overall topology. Conversely, it is possible that entirely different proteins which have no zinc dependency and completely separate function may adopt the zinc endoprotease topology, simply because this fold provides a stable modular scaffold useful in the construction of multidomain proteins. Results of further structural studies are eagerly awaited. 

Figure 3 Cysteine protease and subtilisin-like protease pathways for proneuropeptide processing. Distinct cysteine protease and subtilisin-like protease pathways have been demonstrated for pro-neuropeptide processing. Recent studies have identified secretory vesicle cathepsin L as an important processing enzyme for the production of the endogenous enkephalin opioid peptide. Preference of cathepsin L to cleave at the NH2-terminal side of dibasic residue processing sites yields peptide intermediates with NH2-terminal residues, which are removed by Arg/Lys aminopeptidase. The well-established subtilisin-like protease pathway involves several prohormone convertases (PC). PC1/3 and PC2 have been characterized as neuroendocrine processing proteases. The PC enzymes preferentially cleave at the COOH-terminal side of dibasic processing sites, which results in peptide intermediates with basic residue extensions at their COOH-termini that are removed by carboxypeptidase E/H.

---