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RP2E INRA Université de Lorraine

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Surface plasmon resonance analysis of the binding mechanism of pharmacological and peptidic inhibitors to human somatic Angiotensin I-converting enzyme.

Biochemistry, 52 (48), pp. 8722-8731.

Zidane, F., Zeder-Lutz, G., Altschuh, D., Girardet, J.-M., Miclo, L., Corbier, C., Cakir-Kiefer, C.

2013

Somatic angiotensin I-converting enzyme (ACE) possesses two catalytic domains and plays a major role in the regulation of blood pressure, thus representing a therapeutic target for the treatment of hypertension. We present a comprehensive surface plasmon resonance (SPR) study of the interaction of human somatic ACE with the pharmacological inhibitors captopril and lisinopril, the bradykinin potentiating peptide BPP-11b, and the food peptidic inhibitors from bovine αs2-casein, F(174)ALPQYLK(181) and F(174)ALPQY(179). SPR binding curves recorded with the high potency inhibitors captopril, lisinopril, and BPP-11b were evaluated both by regression analysis and by kinetic distribution analysis. The results indicated that captopril and lisinopril bound ACE with two KD's differing by a factor 10-20 and >30, respectively (lowest KD = 0.1-0.3 nM for both inhibitors). This shows, for the first time in a direct binding assay with the two-domain enzyme, the existence of two binding modes of the pharmacological inhibitors, presumably with the two ACE domains. The BPP-11b-ACE binding curves were complex but showed a predominant interaction with KD in the nanomolar range. The caseinopeptides, known to inhibit ACE with an IC50 of 4.3 μM, bound to ACE with KD = 3-4 μM. Mapping of the F(174)ALPQY(179) binding site on ACE by sequential binding studies using captopril or BPP-11b indicated that it bound to (or near) the two active sites of ACE, in agreement with the stoichiometry of 2 determined from data fitting. Our results provide a detailed characterization of ACE-inhibitor binding modes and validate SPR for predicting the inhibitory potential of new compounds.

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2018

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  • Humusica: Soil biodiversity and global change

    Bulletin of geography: Physical Geography Series, 14 (1), pp. 15-36.

    Zanella, A., Ascher-jenull, J., Ponge, J.F., Bolzonella, C., Banas, D., De nobili, M., Fusaro, S., Sella, L., Giannini, R.

2017

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2016

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2015

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2014

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2013

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