Modular and versatile hybrid coordination motifs on alpha-helical protein surfaces

Inorg Chem. 2010 Aug 2;49(15):7106-15. doi: 10.1021/ic100926g.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cytochromes / chemistry*
  • Cytochromes / metabolism*
  • Models, Molecular
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / metabolism
  • Phenanthrolines / chemistry
  • Protein Stability
  • Protein Structure, Secondary
  • Pyridines / chemistry

Substances

  • Cytochromes
  • Organometallic Compounds
  • Phenanthrolines
  • Pyridines
  • pyridine