Global analysis of heme proteins elucidates the correlation between heme
distortion and 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. We here 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 by 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 and
can inform protein function engineering.