Analogues containing the paramagnetic amino acid TOAC as substrates for angiotensin 1-converting enzyme
Data
2007-05-29
Autores
Teixeira, Luis Gustavo de Deus 
Bersanetti, Patricia Alessandra
Carmona, Adriana Karaoglanovic
Nakaie, Clovis Ryuichi
Tipo
Artigo
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Resumo
The angiotensin I-converting enzyme (ACE) converts the decapeptide angiotensin I (Ang I) into angiotensin II by releasing the C-terminal dipeptide. A novel approach combining enzymatic and electron paramagnetic resonance (EPR) studies was developed to determine the enzyme effect on Ang I containing the paramagnetic 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) at positions 1, 3, 8, and 9. Biological assays indicated that TOAC(1)-Ang I maintained partly the Ang I activity, and that only this derivative and the TOAC(3)-Ang I were cleaved by ACE. Quenching of Tyr(4) fluorescence by TOAC decreased with increasing distance between both residues, suggesting an overall partially extended structure. However, the local bend known to be imposed by the substituted diglycine TOAC is probably responsible for steric hindrance, not allowing the analogues containing TOAC at positions 8 and 9 to act as substrates. in some cases, although substrates and products differ by only two residues, the difference between their EPR spectral lineshapes allows monitoring the enzymatic reaction as a function of time. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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Citação
Febs Letters. Amsterdam: Elsevier B.V., v. 581, n. 13, p. 2411-2415, 2007.