Modular and versatile hybrid coordination motifs on alpha-helical protein surfaces.
We report here the construction of phenanthroline (Phen) and terpyridine (Terpy)-based hybrid coordination motifs (HCMs), which were installed on the surface of the four-helical bundle hemeprotein cytochrome cb(562). The resulting constructs, termed HPhen1, HPhen2, HPhen3, and HTerpy1, feature HCMs that are composed of a histidine ligand and a Phen or Terpy functionality located two helix turns away, yielding stable tri- or tetradentate coordination platforms. Our characterization of the tridentate HCMs indicates that they accommodate many divalent metal ions (Co(2+), Ni(2+), Cu(2+), Zn(2+)) with nanomolar to femtomolar affinities, lead to significant stabilization of the alpha-helical protein scaffold through metal-mediated cross-linking, assert tight control over protein dimerization, and provide stable and high-affinity binding sites for substitution-inert metal probes. Our analyses suggest that such tridentate HCMs may be used modularly on any alpha-helical protein surface in a sequence-independent fashion.
Radford
Robert J
RJ
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr., La Jolla, California 92093-0356, USA.
Nguyen
Phuong C
PC
Tezcan
F Akif
FA
D003580:Cytochromes / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism; D010618:Phenanthrolines / Q000737:chemistry; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011725:Pyridines / Q000737:chemistry
D003580:Cytochromes; D009942:Organometallic Compounds; D010618:Phenanthrolines; D011725:Pyridines; C023666:pyridine