Yarski, Michael A, Bax, Benjamin ![]() |
Abstract
Mouse α- and γ-nerve growth factor (NGF) are glandular kallikreins that form a non-covalent complex (7S NGF) with β-NGF. γ-NGF is an active arginine-specific esteropeptidase; the α-subunit is catalytically inactive and has a zymogen-like conformation. Site-directed mutagenesis of α-NGF to alter the N-terminus and three residues in loop 7, a region that contributes to the catalytic center, restored substantial catalytic activity against N-benzoyl arginine-p-nitroanilide as substrate in two derivatives although they were not as active as recombinant γ-NGF. Seven of the 15 derivatives that remained more α-like were able to substitute for native α-NGF in reforming 7S complexes; the other eight derivatives that were more γ-like showed greatly reduced ability to do so. However, the most γ-like α-NGF derivative could not substitute for native γ-NGF in 7S complex formation. These findings suggest that the α-NGF backbone can be corrected to a functional enzyme by the addition of a normal N-terminal structure and two catalytic site substitutions and that the 7S complex requires one kallikrein subunit in the zymogen form and one in an active conformation.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Publisher: | Elsevier |
ISSN: | 0167-4838 |
Date of Acceptance: | 1 December 1999 |
Last Modified: | 23 Oct 2022 14:03 |
URI: | https://orca.cardiff.ac.uk/id/eprint/112637 |
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