Substrate specificities of growth factor associated kallikreins of the mouse submandibular gland.
The kinetic constants for the hydrolysis of a series of tripeptide p-nitroanilide substrates by mouse epidermal growth factor binding protein (EGF-BP), the gamma-subunit of mouse nerve growth factor (gamma-NGF), bovine pancreatic trypsin (BPT), and porcine pancreatic kallikrein (PPK) have been evaluated. These substrates correspond to the carboxyl-terminal three amino acids of the mature forms of epidermal growth factor ( EGF) and beta-nerve growth factor (beta-NGF), as well as various substitutions in the penultimate and antepenultimate positions, and, as such, represent potential recognition sites for precursor processing. The mouse kallikreins (EGF-BP and gamma-NGF) preferentially hydrolyze the substrates with the sequences of their specifically associated growth factors; however, the constants derived from these reactions do not account for the association constants observed with the mature growth factors, and additional significant binding interactions between EGF-BP and EGF and between gamma-NGF and beta-NGF are predicted to exist outside of the catalytic binding site, i.e., the P3 to P1 positions. A comparison of the kinetic constants of BPT, PPK, and the mouse kallikreins indicates that EGF-BP and gamma-NGF display a hybrid catalytic character. A favorable substrate P1 arginine guanidinium group interaction exists for the mouse kallikreins, similar to that of BPT, but a preference for a hydrophobic side chain in the substrate P2 position makes the mouse kallikreins, especially EGF-BP, more closely resemble PPK than BPT. These findings have significant implications with regard to molecular modeling of the mouse kallikreins.[1]References
- Substrate specificities of growth factor associated kallikreins of the mouse submandibular gland. Blaber, M., Isackson, P.J., Marsters, J.C., Burnier, J.P., Bradshaw, R.A. Biochemistry (1989) [Pubmed]
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