Sulfenamide formation is a conserved mechanism of autoprotection among protein folds

DEFELIPE, LUCAS ALFREDO; LANZAROTTI, ESTEBAN; MARTI, MARCELO ADRIÁN; TURJANSKI, ADRIAN GUSTAVO

Santiago de Chile

Congreso; 2nd ISCB Latin America 2012 Conference on Bioinformatics; 2012

Cysteine oxidation is an important protein regulation mechanism1-3. Oxidation can be reversible or irreversible, self-regulated or by enzymes. The first step in cysteine oxidation is the formation of sulfenic acid which can further oxidize into sulfinic and sulfonic acid or form in some cases reversible cyclic sulfenamides that are able to recover cysteine via selfregulation. Nevertheless structural determinants that allow the formation of cyclic sulfenamides are still unknown. Using a structural database developed by our group and literature analysis we found a strong correlation between an unfavorable psi dihedral angle conformation of the cysteine residue and its tendency to suffer sulfenamide and sulfenic acid oxidation finding 150 proteins with these properties. Through an analysis of the database results a structural motif consisting in an α helix-β sheet-turn-α helix was found in 5 different PFAM families (PFAM00102, PFAM00117, PFAM00581, PFAM00782, PFAM01174 y PF01965) some of these families have reported cysteine oxidation1-5. In order to get insight into the chemical and structural changes necessary for sulfenamide formation a QM-MM reaction was performed in PTP1B protein. The reaction mechanism requires the backbone amide group of the next aminoacid from the cysteine to form a hydrogen bond with the oxygen atom of the sulfenic acid which is only observed in the psi anomalous conformation. This structural motif is related to the ability to protect the protein from oxidative stress and is a more general mechanism than previously thought.