Mutation effects on charge transport through the p58c iron–sulfur protein

Abstract

Functional electron transfer between the [Fe4S4] cluster and the nucleic acid is impacted by a Y345C mutation in the p58c subunit of human primase.

Correlation between Charge Transport and Base Excision Repair in the MutY–DNA Glycosylase

“…MD simulations (using NAMD 2.11) of the wild-type (WT) MutY–DNA complex were performed using the A 2+ and A 3+ force fields (FFs) reported in ref . for the [Fe 4 S 4 ] 2+ and [Fe 4 S 4 ] 3+ clusters.…”

“…Ideally, the FFs used in the MD simulation should be updated as the charge hops from the hole donor in the DNA to the iron–sulfur cluster. As we recently observed, a more practical MD approach is to analyze the dynamics of the protein–DNA complex using both the A 2+ and the A 3+ FFs, while reactive FFs that allow for bond breaking and formation were not considered for the purposes of this study that focuses on electron–hole transfer . The FF parameters for the oxoG moiety were obtained from ref .…”

How the Donor/Acceptor Spin States Affect the Electronic Couplings in Molecular Charge-Transfer Processes?

“…The authors calculate electronic coupling matrix elements for the biological ET process that involves iron–sulfur clusters. Teo et al performed both static DFT 26 and molecular dynamics simulations 27 of charge transport between a protein-containing iron–sulfur cluster and the DNA double strain. In any case, a complicated electronic structure of [Fe 4 S 4 ] clusters was covered in an approximate way using a broken-symmetry approach to couple individual high-spin (HS) Fe +2/+3 centers to overall low-spin (LS), antiferromagnetic states.…”

Why Do Most Aromatics Fail to Support Hole Hopping in the Cytochrome c Peroxidase–Cytochrome c Complex?

“…The time scales for molecular recognition and docking, conformational change, tunneling, and multi-step hopping can all influence what is observed experimentally. 14,[16][17][18] Rates may be limited by familiar electron transfer factors like activation free energies and tunneling distances, or by protein conformational change. 19,20 Potential transitions between single-step tunneling and multi-step hopping, as well as transitions from activation control to conformational gating control can lead to controversies in interpreting experimental kinetic data.…”

“…Charge hopping through aromatic amino acids occurs in many biological redox systems, including photosystem II, ribonucleotide reductase, and photolyase. − DNA charge transport, oxidative damage protection, redox signaling, and bioenergetic redox chains are also believed to exploit hole hopping through aromatic species. − A challenge faced in describing multiprotein electron transfer is to understand the combination of factors that contribute to the kinetics. The time scales for molecular recognition and docking, conformational change, tunneling, and multistep hopping can all influence what is observed experimentally. ,− Rates may be limited by familiar electron transfer factors such as activation free energies and tunneling distances, or by protein conformational change. , Potential transitions between single-step tunneling and multistep hopping, as well as transitions from activation control to conformational gating control can lead to controversies in interpreting experimental kinetic data. The interplay among the many factors that may underpin biological electron transfer kinetics makes these reactions rich and diverse. ,− …”