title: Re-evaluation of amino acid sequence and structural consensus rules for cysteine-nitric oxide reactivity.
abstract: 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 Cys beta93-nitrosylation and Cys beta393NO-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-Sy atomic structural microenvironment rather than on the tri- or tetra-peptide sequence consensus motif.
authors.affiliation: Department of Biology, University Roma Tre, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ascenzi
authors.forename: M
authors.initials: M
authors.lastname: Colasanti
authors.forename: T
authors.initials: T
authors.lastname: Persichini
authors.forename: M
authors.initials: M
authors.lastname: Muolo
authors.forename: F
authors.initials: F
authors.lastname: Polticelli
authors.forename: G
authors.initials: G
authors.lastname: Venturini
authors.forename: D
authors.initials: D
authors.lastname: Bordo
authors.forename: M
authors.initials: M
authors.lastname: Bolognesi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000737:chemistry*; D005069:Evaluation Studies as Topic; D006801:Humans; D009569:Nitric Oxide / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D009569:Nitric Oxide; D003545:Cysteine