title: Atropisomerism of the Asn α radicals revealed by Ramachandran surface topology.
abstract: C radicals are typically trigonal planar and thus achiral, regardless of whether they originate from a chiral or an achiral C-atom (e.g., C-H + (•)OH → C• + H2O). Oxidative stress could initiate radical formation in proteins when, for example, the H-atom is abstracted from the Cα-carbon of an amino acid residue. Electronic structure calculations show that such a radical remains achiral when formed from the achiral Gly, or the chiral but small Ala residues. However, when longer side-chain containing proteogenic amino acid residues are studied (e.g., Asn), they provide radicals of axis chirality, which in turn leads to atropisomerism observed for the first time for peptides. The two enantiomeric extended backbone structures, •βL and •βD, interconvert via a pair of enantiotopic reaction paths, monitored on a 4D Ramachandran surface, with two distinct transition states of very different Gibbs-free energies: 37.4 and 67.7 kJ/mol, respectively. This discovery requires the reassessment of our understanding on radical formation and their conformational and stereochemical behavior. Furthermore, the atropisomerism of proteogenic amino acid residues should affect our understanding on radicals in biological systems and, thus, reframes the role of the D-residues as markers of molecular aging.
authors.affiliation: Department of Chemical Informatics, Faculty of Education, University of Szeged , 6726 Szeged, Hungary.
authors.forename: Klára Z
authors.initials: KZ
authors.lastname: Gerlei
authors.forename: Imre
authors.initials: I
authors.lastname: Jákli
authors.forename: Milán
authors.initials: M
authors.lastname: Szőri
authors.forename: Svend J Knak
authors.initials: SJ
authors.lastname: Jensen
authors.forename: Béla
authors.initials: B
authors.lastname: Viskolcz
authors.forename: Imre G
authors.initials: IG
authors.lastname: Csizmadia
authors.forename: András
authors.initials: A
authors.lastname: Perczel
mesh_terms: D001216:Asparagine / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D005609:Free Radicals; D010455:Peptides; D001216:Asparagine