The Impact of Second Coordination Sphere Methionine-Aromatic Interactions in Copper Proteins
- Brooklyn P. Fedoretz-MaxwellBrooklyn P. Fedoretz-MaxwellDepartment of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, CanadaMore by Brooklyn P. Fedoretz-Maxwell
- Catherine H. ShinCatherine H. ShinDepartment of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, CanadaMore by Catherine H. Shin
- Gregory A. MacNeilGregory A. MacNeilDepartment of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, CanadaMore by Gregory A. MacNeil
- Liam J. WorrallLiam J. WorrallDepartment of Biochemistry and Molecular Biology and Centre for Blood Research, University of British Columbia, Vancouver, British Columbia V6T 1Z3, CanadaMore by Liam J. Worrall
- Rachel ParkRachel ParkMore by Rachel Park
- Natalie C. J. Strynadka
- Charles J. Walsby
- , and
- Jeffrey J. Warren*
The interplay between the primary and secondary coordination spheres in biological metal sites plays an essential role in controlling their properties. Some of the clearest examples of this are from copper sites in blue and purple copper proteins. Many such proteins contain methionine (Met) in the primary coordination sphere as a weakly bound ligand to Cu. While the effects of replacing the coordinated Met are understood, less so is the importance of its second-sphere interactions. In this combined informatics and experimental study, we first present a bioinformatics investigation of the second-sphere environments in biological Met-Cu motifs. The most common interaction is between the Met-CH3 and the π-face of a phenylalanine (Phe) (81% of surveyed structures), tyrosine (Tyr) (11%), and tryptophan (Trp) (8%). In most cases, the Met-CH3 also forms a contact with a π-face of one of a Cu-ligating histidine-imidazole. Such interactions are widely distributed in different Cu proteins. Second, to explore the impact of the second-sphere interactions of Met, a series of artificial Pseudomonas aeruginosa azurin proteins were produced where the native Phe15 was replaced with Tyr or Trp. The proteins were characterized using optical and magnetic resonance spectroscopies, X-ray diffraction, electrochemistry, and an investigation of the time-resolved electron-transfer kinetics of photosensitizer-modified proteins. The influence of the Cu-Met-Aro interaction on azurin’s physical properties is subtle, and the hallmarks of the azurin blue copper site are maintained. In the Phe15Trp variant, the mutation to Phe15 induces changes in Cu properties that are comparable to replacement of the weak Met ligand. The broader impacts of these widely distributed interactions are discussed.
This article is cited by 2 publications.
- Curtis A. Gibbs, Brooklyn P. Fedoretz-Maxwell, Gregory A. MacNeil, Charles J. Walsby, Jeffrey J. Warren. Proximal Methionine Amino Acid Residue Affects the Properties of Redox-Active Tryptophan in an Artificial Model Protein. ACS Omega 2023, 8 (22) , 19798-19806. https://doi.org/10.1021/acsomega.3c01589
- Yusuke Tomita, Taka-aki Okamura, Yuki Umeda, Koichiro Nishimoto, Satoshi Yamashita, Kiyotaka Onitsuka. Syntheses and Structures of Arenethiolato Cobalt(II) Complexes Containing Acylamino Groups: Steric Effects of Bulky Ligands on Coordination and Geometry. Inorganic Chemistry 2023, 62 (22) , 8678-8691. https://doi.org/10.1021/acs.inorgchem.3c00849