title: Surface residues dynamically organize water bridges to enhance electron transfer between proteins.
abstract: Cellular energy production depends on electron transfer (ET) between proteins. In this theoretical study, we investigate the impact of structural and conformational variations on the electronic coupling between the redox proteins methylamine dehydrogenase and amicyanin from Paracoccus denitrificans. We used molecular dynamics simulations to generate configurations over a duration of 40 ns (sampled at 100-fs intervals) in conjunction with an ET pathway analysis to estimate the ET coupling strength of each configuration. In the wild-type complex, we find that the most frequently occurring molecular configurations afford superior electronic coupling due to the consistent presence of a water molecule hydrogen-bonded between the donor and acceptor sites. We attribute the persistence of this water bridge to a "molecular breakwater" composed of several hydrophobic residues surrounding the acceptor site. The breakwater supports the function of nearby solvent-organizing residues by limiting the exchange of water molecules between the sterically constrained ET region and the more turbulent surrounding bulk. When the breakwater is affected by a mutation, bulk solvent molecules disrupt the water bridge, resulting in reduced electronic coupling that is consistent with recent experimental findings. Our analysis suggests that, in addition to enabling the association and docking of the proteins, surface residues stabilize and control interprotein solvent dynamics in a concerted way.
authors.affiliation: Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada, T2N 1N4.
authors.forename: Aurélien
authors.initials: A
authors.lastname: de la Lande
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Babcock
authors.forename: Jan
authors.initials: J
authors.lastname: Rezác
authors.forename: Barry C
authors.initials: BC
authors.lastname: Sanders
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Salahub
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055592:Biophysical Phenomena; D004579:Electron Transport; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010231:Paracoccus denitrificans / Q000201:enzymology / Q000235:genetics; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012997:Solvents; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D011506:Proteins; D011994:Recombinant Proteins; D012997:Solvents; D014867:Water; C021567:methylamine dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors