Global Analysis of Heme Proteins Elucidates the Correlation between Heme Distortion and the Heme-Binding Pocket

Heme
proteins play diverse and important biological roles, from
electron transfer and chemical catalysis to oxygen transport and/or
storage. Although the distortion of heme porphyrin correlates with
the physical properties of heme, such as the redox potential and oxygen
affinity, the relationship between heme distortion and the heme protein
environment is unclear. Here, we tested the hypothesis that the protein
environment of the heme-binding pocket determines heme distortion
(conformation). We analyzed the correlations between the amino acid
composition of the heme-binding pocket and the magnitude of heme distortion
along 12 vibrational modes using machine learning. A correlation was
detected in the three lowest vibrational modes. Analysis of heme distortions
in nearly the same environments of the heme-binding pocket supported
this notion. Our analyses indicate that the heme-binding pocket environment
is a major factor impacting the distortion of heme porphyrin along
the three lowest vibrational modes. In addition, statistical analysis
of the distortion of heme porphyrin revealed that the peaks of distributions
of the ruffling and breathing distortions are shifted from 0 (the
equilibrium structure). Both the ruffling and breathing distortions
are correlated with the redox potential of heme, so that heme molecules
with these distortions have a lower redox potential than planar molecules.
These findings explain the structure–function relationship
of heme.