360 IRON-CONTAINING PROTEINS AND ENZYMES
Cytochrome researchers often cite R. P. Ambler ’ s work on classifying cyto-
chromes c (discussed here in Section 7.7 ).^27 Recently, Ivano Bertini and co -
workers published a review of cytochromes c, using a bioinformatics approach
to “ collect all the sequences of cytochrome c domains in available genome
sequences. ”^28 This work included some helpful notes on cytochrome c nomen-
clature. The term “ cytochrome ” may have been fi rst mentioned by Keilin in
1925 to describe a group of heme proteins that could undergo oxidation –
reduction reactions.^29 These proteins were characterized by their red color and
intense absorption bands in the 510 - to 615 - nm range. As different cyto-
chromes c were characterized, they were classifi ed in two ways: (1) According
to functional class (c 1 , c 2 , c 3 , and so on; these criteria have not been applied
consistently over time) and (2) according to subscripts assigned based on the
experimental wavelength in nanometers of the so - called α - band in the visible
absorption spectrum of the reduced protein (c 550 , c 552 , and so on). The most
recent attempt on a systematic nomenclature for cytochromes c was published
by the International Union of Biochemistry and Molecular Biology in 1989.^30
The reference 28 authors have collected this information in Table 6 of their
publication. The table lists the number of hemes in each cytochrome c as well
as the iron ion ’ s axial ligands and its Ambler classifi cation.^27 Cytochromes are
generally six - coordinate and low - spin in both the Fe(III) and Fe(II) oxidation
states, but there are many exceptions to this rule. For instance, cyotchrome c ′
is a high - spin cytochrome c, widely distributed in bacteria with a typical cyto-
chrome c fold — that is, a four α - helix bundle enclosing a single heme. It is
unusual in that it usually exists as a dimer and the heme ’ s iron atom is penta-
coordinate with a single histidine axial ligand.
In a 2004 Chemical Reviews article, F. A. Walker discussed the geometric
and electronic structure of hemes in relation to their spectroscopic footprints
and their reduction potentials.^31 As an example of the large number of possible
variables, she summarized the factors that affect cytochromes c as (1) the type
of axial ligands bound to the heme (his - met for mitochondrial and bacterial
cytochromes c, his – his for cytochromes c 3 and other multi - heme cytochromes),
(2) the orientation of axial ligands that not only have anσ - donor electron pair
but also have aπ - donor orbital perpendicular to the σ - donor orbital (examples
are his, met, cys), (3) the solvent accessibility of the heme, (4) surface and
buried charged groups near the heme plus the overall charge type of the sur-
rounding protein or opposite charges on its partner protein, (5) the dipoles of
the protein backbone and side chains, (6) changes in protein conformation and
amino acid residue protonation, and (7) solvent pH. In this text ’ s discussion,
we will concentrate on eukaryotic mitochondrial cytochrome c.
In mid - 2006, a search of the Jena Library for cytochrome b returned 197
entries, including those described in Sections 7.5 (cytochrome b 6 f) and 7.6
(cytochrome bc 1 ). Cytochrome b contains the heme b subunit (heme proto-
porphyrin IX), the same metal cofactor contained in hemoglobin and myoglo-
bin (see Figure 7.1 ). Other cytochrome b subunits occur in the cytochrome b 6 f
complex, also known as plasotquinol : plastocyanin reductase (EC 1.10.22) and