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The Mechanism of Papain Inhibition by Peptidyl Aldehydes by Michael Shokhen; Netaly Khazanov; Amnon Albeck is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract Various mechanisms for the reversible formation of a covalent tetrahedral complex (TC) between papain and peptidyl aldehyde inhibitors were simulated by DFT calculations, applying the quantum mechanical/self consistent reaction field (virtual solvent) [QM/SCRF(VS)] approach. Only one mechanism correlates with the experimental kinetic data. The His–Cys catalytic diad is in an N/SH protonation state in the noncovalent papain–aldehyde Michaelis complex. His159 functions as a general base catalyst, abstracting a proton from the Cys25, whereas the activated thiolate synchronously attacks the inhibitor's carbonyl group. The final product of papain inhibition is the protonated neutral form of the hemithioacetal TC(OH), in agreement with experimental data. The predicted activation barrier __g__ = 5.2 kcal mol^−1^ is close to the experimental value of 6.9 kcal mol^−1^. An interpretation of the experimentally observed slow binding effect for peptidyl aldehyde inhibitors is presented. The calculated __g__ is much lower than the rate determining activation barrier of hemithioacetal formation in water, __g__, in agreement with the concept that the preorganized electrostatic environm

Who reads The Mechanism of Papain Inhibition by Peptidyl Aldehydes?

Author

Michael Shokhen; Netaly Khazanov; Amnon Albeck

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); Wiley-Liss Inc; Wiley (ISSN 0887-3585)

Published

2010

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)