Re-evaluation of amino acid sequence and structural consensus rules for cysteine-nitric oxide reactivity

P. Ascenzi, M. Colasanti, T. Persichini, M. Muolo, F. Polticelli, G. Venturini, D. Bordo, M. Bolognesi

Research output: Contribution to journalArticlepeer-review


Nitric oxide (NO), produced in different cell types through the conversion of L-arginine into L-citrulline by the enzyme NO synthase, has been proposed to exert its action in several physiological and pathological events. The great propensity for nitrosothiol formation and breakdown represents a mechanism which modulates the action of macromolecules containing NO-reactive Cys residues at their active centre and/or allosteric sites. Based on the human haemoglobin (Hb) structure and accounting for the known acid-base catalysed Cysβ93-nitrosylation and Cysβ93NO-denitrosylation processes, the putative amino acid sequence (Lys/Arg/His/Asp/Glu)Cys(Asp/Glu) (sites - 1, 0, and + 1, respectively) has been proposed as the minimum consensus motif for Cys-NO reactivity. Although not found in human Hb, the presence of a polar amino acid residue (Gly/Ser/Thr/Cys/Tyr/Asn/Gln) at the -2 position has been observed in some NO-reactive protein sequences (e.g., NMDA receptors). However, the most important component of the tri- or tetra-peptide consensus motif has been recognised as the Cys(Asp/Glu) pair [Stamler et al., Neuron (1997) 18, 691-696]. Here, we analyse the three-dimensional structure of several proteins containing NO-reactive Cys residues, and show that their nitrosylation and denitrosylation processes may depend on the Cys-Sγ atomic structural microenvironment rather than on the tri- or tetra-peptide sequence consensus motif.

Original languageEnglish
Pages (from-to)623-627
Number of pages5
JournalBiological Chemistry
Issue number7
Publication statusPublished - 2000


  • Acid-base catalysis
  • Amino acid sequence consensus rules
  • Cys-nitrosylation
  • CysNO-denitrosylation
  • Nitric oxide
  • Structural consensus rules

ASJC Scopus subject areas

  • Biochemistry


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