Pseudo-enzymatic hydrolysis of 4-nitrophenyl myristate by human serum albumin

Biochemical and Biophysical Research Communications
Paolo Ascenzi, Mauro Fasano

Abstract

Most of the esterase properties of human serum albumin (HSA) are the result of multiple irreversible chemical modifications rather than turnover. The HSA-catalyzed hydrolysis of 4-nitrophenyl myristate (NphOMy) is consistent with the minimum three-step mechanism involving the acyl-enzyme intermediate HSA-OMy: Under all the experimental conditions, values of K(s) (= k(-1)/k(+1)), k(+2), and k(+2)/K(s) determined under conditions where [HSA] ≥ 5 × [NphOMy] and [NphOMy] ≥ 5 × [HSA] match very well each other. The deacylation process is rate limiting in catalysis (i.e., k(+3) < k(+2)) and k(-2)~k(-3)~0 s(-1). The pH dependence of k(+2)/K(s), k(+2), and K(s) reflects the acidic pK(a)-shift of one ionizing group from 8.9 ± 0.2 in NphOMy-free HSA to 6.8 ± 0.3 in the HSA:NphOMy adduct. The HSA-catalyzed hydrolysis of NphOMy is inhibited competitively by diazepam, indicating that Tyr411 is the active-site nucleophile.

References

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Sep 20, 2005·Journal of Molecular Biology·Jamie GhumanStephen Curry
Jan 6, 2006·IUBMB Life·Mauro FasanoPaolo Ascenzi
Sep 12, 2009·Drug Metabolism and Pharmacokinetics·Stephen Curry
May 11, 2011·IUBMB Life·Gabriella FanaliMauro Fasano
Jan 11, 2012·Molecular Aspects of Medicine·Gabriella FanaliPaolo Ascenzi

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Citations

Dec 25, 2012·Journal of Pharmaceutical and Biomedical Analysis·Haibo ShenJuan Qi
Jul 10, 2012·Biochemical and Biophysical Research Communications·Paolo AscenziMauro Fasano
Feb 26, 2013·British Journal of Haematology·Yaser A DiabNaomi L C Luban
Jul 15, 2015·Bioorganicheskaia khimiia·N V GoncharovA I Ukolov
Jul 19, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nikolay V GoncharovPavel V Avdonin

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