Prohormone or proprotein convertases (PC2) are members of the subtilisin family of serine proteases. They are involved in the activation of precursor molecules by endoproteolytic cleavage at basic amino acid residues within the general motif (K/R)-(X)n- (K/R)2, where n is 0, 2, 4 or 6 and X is usually not Cys. Among the members of this prohormone convertase family, Neuroendocrine Convertase-2 (NEC-2) is regarded as one of the important proteins involved in the maturation of many precursor proteins. Being widely distributed in the neuroendocrine cells, these proteins play a vital role in causing malignant gliomas. They can serve as important drug targets in the treatment of cancers. In the present study, a 3D model of NEC-2 was generated using homology modeling. The model was optimized by a brief energy minimization in CHARMM and dynamics simulation of 250ps in MOE. The validation results of PROCHECK and Profile 3D show that the stereochemical quality of the model is good. The Calpha backbone of the template and the target (NEC-2) when superimposed showed RMSD of 0.39A. The model showed Asp51, His92 and Ser268 in the active site as seen in most of the PC2 members. The NEC-2 structure differs from that of furin at the catalytic pocket region with relevance to the amino acid composition which can be exploited for the design of specific inhibitors towards NEC-2.

Cerebellar granular neurons were grown in culture up to 21 days and the protein compositions of undifferentiated (day 1), partially differentiated (day 7) and fully differentiated (day 21) neurons were analyzed by high-resolution 2D-gel electrophoresis. During neuronal differentiation there were not only increase in the amount of several known proteins, viz. actin, tubulin (both alpha and beta subunits), myosin (heavy and light chains), but very interesting changes were also observed in the expressions of different subunits and isoforms of those proteins. Furthermore, both in the acidic (pI 4.0-4.5) and alkaline (pI 7.0-8.5) regions interesting up and down regulations of several unidentified proteins were observed during the neuronal differentiation. These results indicated that there were several unidentified proteins that might be very valuable targets for studying regulation of neuronal differentiation. Research is going on for further characterization of those proteins using recently developed proteomics technology.