Structural Consensus Rules for Cysteine Protease Inhibition by NO(-Donors)

Title: Structural Consensus Rules for Cysteine Protease Inhibition by NO(-Donors)

Volume: 1 Issue: 3

Author(s): Paolo Ascenzi, Alessio Bocedi, Fabio Polticelli and Martino Bolognesi

Affiliation:

Keywords: nitric oxide, cysteine protease, enzyme inhibition, cys-nitrosylation, cysno-denitrosylation, acid-base catalysis, structural consensus rules

Abstract: Nitric oxide (NO) exerts its action in several physiological and pathological events. The great propensity for Cys(NO)-(de)nitrosylation represents a mechanism which modulates cysteine protease action. Cys(NO)-(de)nitrosylation is assisted by basic and acid residues, within the environment of the Cys catalytic residue. In particular, Cys-nitrosylation is catalyzed by amino acid residues which stabilize the reactive deprotonated form of the Cys Sγ atom. By contrast, CysNO-denitrosylation is assisted by amino acid residues which facilitate the protonation of the Cys Sγ atom with the concomitant NO release. Note that Cysnitrosylated residues may undergo oxidation giving rise to sulfenic, sulfinic or sulfonic acid and lead to the formation of disulfide bridges. These structural consensus rules apply not only to cysteine proteases, but represent a generally accepted mechanism for (macro)molecular Cys(NO)-(de)nitrosylation.

Cite this article as:

Ascenzi Paolo, Bocedi Alessio, Polticelli Fabio and Bolognesi Martino, Structural Consensus Rules for Cysteine Protease Inhibition by NO(-Donors), Current Enzyme Inhibition 2005; 1 (3) . https://dx.doi.org/10.2174/157340805774580448

DOI https://dx.doi.org/10.2174/157340805774580448	Print ISSN 1573-4080
Publisher Name Bentham Science Publisher	Online ISSN 1875-6662