Probing the function of heme distortion in the H-NOX family

ACS Chem Biol. 2008 Nov 21;3(11):703-10. doi: 10.1021/cb800185h.

Abstract

Hemoproteins carry out diverse functions utilizing a wide range of chemical reactivity while employing the same heme prosthetic group. It is clear from high-resolution crystal structures and biochemical studies that protein-bound hemes are not planar and adopt diverse conformations. The crystal structure of an H-NOX domain from Thermoanaerobacter tengcongensis (Tt H-NOX) contains the most distorted heme reported to date. In this study, Tt H-NOX was engineered to adopt a flatter heme by mutating proline 115, a conserved residue in the H-NOX family, to alanine. Decreasing heme distortion in Tt H-NOX increases affinity for oxygen and decreases the reduction potential of the heme iron. Additionally, flattening the heme is associated with significant shifts in the N-terminus of the protein. These results show a clear link between the heme conformation and Tt H-NOX structure and demonstrate that heme distortion is an important determinant for maintaining biochemical properties in H-NOX proteins.

Publication types

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

MeSH terms

  • Bacterial Proteins / chemistry
  • Heme / chemistry*
  • Hemeproteins / chemistry*
  • Hemeproteins / genetics
  • Molecular Conformation
  • Mutagenesis, Site-Directed
  • Oxygen / metabolism
  • Protein Binding
  • Protein Conformation
  • Thermoanaerobacter / chemistry*

Substances

  • Bacterial Proteins
  • Hemeproteins
  • Heme
  • Oxygen