Probing the function of heme distortion in the H-NOX family.
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.
Olea
Charles
C
Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, California 94720, USA.
Boon
Elizabeth M
EM
Pellicena
Patricia
P
Kuriyan
John
J
Marletta
Michael A
MA
D001426:Bacterial Proteins / Q000737:chemistry; D006418:Heme / Q000737:chemistry*; D006420:Hemeproteins / Q000737:chemistry* / Q000235:genetics; D008968:Molecular Conformation; D016297:Mutagenesis, Site-Directed; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D046968:Thermoanaerobacter / Q000737:chemistry*
D001426:Bacterial Proteins; D006420:Hemeproteins; D006418:Heme; D010100:Oxygen