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Nerve growth factor α subunit: effect of site-directed mutations on catalytic activity and 7S NGF complex formation

Yarski, Michael A, Bax, Benjamin, Hogue-Angeletti, Ruth A and Bradshaw, Ralph A 2000. Nerve growth factor α subunit: effect of site-directed mutations on catalytic activity and 7S NGF complex formation. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 1477 (1-2) , pp. 253-266. 10.1016/S0167-4838(99)00277-0

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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
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 0167-4838
Date of Acceptance: 1 December 1999
Last Modified: 16 Jul 2018 15:11
URI: http://orca.cardiff.ac.uk/id/eprint/112637

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