Darwin at the molecular scale: selection and variance in electron tunnelling proteins including cytochrome c oxidase
- 12 July 2006
- journal article
- review article
- Published by The Royal Society in Philosophical Transactions B
- Vol. 361 (1472), 1295-1305
- https://doi.org/10.1098/rstb.2006.1868
Abstract
Biological electron transfer is designed to connect catalytic clusters by chains of redox cofactors. A review of the characterized natural redox proteins with a critical eye for molecular scale measurement of variation and selection related to physiological function shows no statistically significant differences in the protein medium lying between cofactors engaged in physiologically beneficial or detrimental electron transfer. Instead, control of electron tunnelling over long distances relies overwhelmingly on less than 14 Å spacing between the cofactors in a chain. Near catalytic clusters, shorter distances (commonly less than 7 Å) appear to be selected to generate tunnelling frequencies sufficiently high to scale the barriers of multi-electron, bond-forming/-breaking catalysis at physiological rates. We illustrate this behaviour in a tunnelling network analysis of cytochrome c oxidase. In order to surmount the large, thermally activated, adiabatic barriers in the 5–10 kcal mol −1 range expected for H + motion and O 2 reduction at the binuclear centre of oxidase on the 10 3 –10 5 s −1 time-scale of respiration, electron access with a tunnelling frequency of 10 9 or 10 10 s −1 is required. This is provided by selecting closely placed redox centres, such as haem a (6.9 Å) or tyrosine (4.9 Å). A corollary is that more distantly placed redox centres, such as Cu A , cannot rapidly scale the catalytic site barrier, but must send their electrons through more closely placed centres, avoiding direct short circuits that might circumvent proton pumping coupled to haems a to a 3 electron transfer. The selection of distances and energetic barriers directs electron transfer from Cu A to haem a rather than a 3 , without any need for delicate engineering of the protein medium to ‘hard wire’ electron transfer. Indeed, an examination of a large number of oxidoreductases provides no evidence of such naturally selected wiring of electron tunnelling pathways.Keywords
This publication has 56 references indexed in Scilit:
- Are Acidic and Basic Groups in Buried Proteins Predicted to be Ionized?Journal of Molecular Biology, 2005
- Simulating redox coupled proton transfer in cytochromecoxidase: Looking for the proton bottleneckFEBS Letters, 2005
- Theoretical Study of the Energetics of Proton Pumping and Oxygen Reduction in Cytochrome OxidaseThe Journal of Physical Chemistry B, 2003
- The Dependence of the Initial Electron-Transfer Rate on Driving Force in Rhodobacter sphaeroides Reaction CentersThe Journal of Physical Chemistry B, 2002
- The Nature of Tunneling Pathway and Average Packing Density Models for Protein-Mediated Electron TransferThe Journal of Physical Chemistry A, 2002
- Intramolecular electron transfer in cytochrome c oxidase: a cascade of equilibriaBiochemistry, 1992
- Tunneling pathway and redox-state-dependent electronic couplings at nearly fixed distance in electron transfer proteinsThe Journal of Physical Chemistry, 1992
- Internal electron transfer in cytochrome c oxidase: evidence for a rapid equilibrium between cytochrome a and the bimetallic siteBiochemistry, 1991
- Electron transfer in spinach photosystem I reaction center containing benzo‐, naphtho‐ and anthraquinones in place of phylloquinoneFEBS Letters, 1989
- Electron transfers in chemistry and biologyBiochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics, 1985