Huge Disulfide-Linkage’S Electron Capture Variation Induced by α-Helix Orientation
Résumé
An active site containing a Cys-X-X-Cys motif (CXXC), where X denotes any amino acid, is always found in the thiol-disulfide oxidoreductase superfamily. Because of its very high propensity for N-termini of α-helices, we examine the effect of this secondary structure on the disulfide-linked CXXC electron affinity. A Cys-Gly-Pro-Cys motif (CGPC) is chosen as an example, as it is the canonical motif found in thioredoxins. QM/MM calculations (MP2/6−31+G**:CHARMM) establish that the electron capture is strongly favored by an N-terminal α-helix, due to the positive electrostatic potential in the vicinity of the active site. The enhancement of adiabatic electron affinity accounts for ca. 0.9 eV for a 12-residues helix and rapidly converges as the number of alanine residues increases. A close agreement between a reference thioredoxin (Trx h) and the corresponding model peptide is found (respectively +2.20 and +2.12 eV), in parallel with experimental redox potentials [Iqbalsyah et al. Protein Sci. 2006, 15, 2026−2030]. This suggests a simple additive rule for geometrical and electrostatic effects. The electron affinity of the CXXC active site is first considered in an isolated way. Then, the strong modulation of the electrostatic field created by the α-helix can be added up. This simple partition scheme allows a proper quantification of the ease of attachment of a low-energy electron.