Studies on the subsite specificity of rat nardilysin (N-arginine dibasic convertase)

Studies on the subsite specificity of rat nardilysin (N-arginine dibasic convertase)

Author Chow, K. M. Google Scholar
Csuhai, E. Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
St Pyrek, J. Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Hersh, L. B. Google Scholar
Institution Univ Kentucky
Universidade Federal de São Paulo (UNIFESP)
Transylvania Univ
Abstract The subsite specificity of rat nardilysin was investigated using fluorogenic substrates of the type 2-amino-benzoyl-GGX(1)X(2)RKX(3)GQ-ethylenediamine-2,4-dinitrophenyl, where P-2, P-2', and P-3 residues were varied. (The nomenclature of Schechter and Berger (Schechter, L, and Berger, A. (1967) Biochem, Biophys, Res. Commun, 27, 157-162) is used where cleavage of a peptide occurs between the P-1 and P-1' residues, and adjacent residues are designated P-2, P-3, P-2', P-3', etc.) There was little effect on II, among different residues at any of these positions, in contrast, residues at each position affected k(cat), with P-2 residues having the greatest effect, the S-3, S-2, and S-2' subsites differed in their amino acid preference, Tryptophan and serine, which produced poor substrates at the P-2 position, were among the best P-2' residues, the specificity at P-3 was generally opposite that of P-2. Residues at P-2, and to a lesser extent at P-3, influenced the cleavage site. At the P-2 position, His, Phe, Tyr,Asn, or Trp produced cleavage at the amino side of the first basic residue. in contrast, a P-2 Ile or Val produced cleavage between the dibasic pair, Other residues produced intermediate effects, the pH dependence for substrate binding showed that the enzyme prefers to bind a protonated histidine, A comparison of the effect of arginine or lysine at the P-1' or P-1 position showed that there is a tendency to cleave on the amino side of arginine and that this cleavage produces the highest k(cat) values.
Language English
Date 2000-06-30
Published in Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 275, n. 26, p. 19545-19551, 2000.
ISSN 0021-9258 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Biochemistry Molecular Biology Inc
Extent 19545-19551
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000087941300017

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