CYTOCHROMES c 411
synthesis from ADP. The bc 1 complex contains a c 1 - type cytochrome (detailed
in Section 7.6) that differs from cytochrome c in several ways. First, the bc 1
complex c - type cytochrome is a much larger protein of about 200 residues that
contains at least one transmembrane helix. Normally, cytochrome c proteins
reside in the cytoplasm outside the cytoplasmic membrane of prokaryotes, in
the intermembrane space of mitochondria, or in the lumen of chloroplasts.^99
The bc 1 complex is also identifi ed in the literature as the ubiquinol/cytochrome
c oxidoreductase or the QCR. The interactions between cytochrome c and the
bc 1 complex have been extensively studied, and electron transfer partnership
between the two has been described.^108 Much less is known about the interac-
tions between cytochrome c oxidase (Section 7.8) and cytochrome c.
7.7.2 Mitochondrial Cytochrome c (Yeast),
Mitochondrial cytochrome c has been studied in eukaryotes such as yeast,
tuna, and horse. Yeast iso - 1 cytochrome c was the subject of X - ray crystallo-
graphic studies beginning in the 1990s. The Gary D. Brayer research group
published early crystallographic structures of yeast iso - 1 - ferrocytochrome
c (Fe(II)) (PDB: 1YCC)^109 and iso - 1 - ferricytochrome c (Fe(III)) (PDB:
2YCC).^110 The Fe(II) PDB: 1YCC structure refi ned to a resolution of 1.23 Å.
The molecule exhibited a typical cytochrome c fold with the c - type heme being
held in place by covalent linkages between cysteine S δ thiolates and vinylic
carbons of the protoporphyrin IX heme ligand in a CXXXH pattern. In this
yeast iso - 1 cytochrome c, the CXXCH pattern involved cys14 – leu15 – gln16 –
cys17 – his18. The heme ’ s Fe(II) ligand carries the N ε 2 atom of his18 as one axial
ligand (N ε 2 – Fe = 1.99 Å ) and the S δ atom of met80 as the other (S δ – Fe = 2.35 Å )
(see Figure 7.33 and Table 7.8 ). The protein ’ s secondary structure organizes
into a series ofα - helices and reverse turns that envelop the heme prosthetic
group in a hydrophobic pocket. In their local environment, the α - helices are
sometimes distorted, especially near intrahelical threonine residues. See, for
example, the region surrounding thr69, colored red in the lower center of
Figure 7.33. In Figure 7.33 , the secondary structure is shown in cartoon format
with the PDB: 1YCC structure colored green and the PDB: 2YCC structure
colored cyan. The heme prosthetic group, the axial ligands his 18 and met80,
and selected important hydrogen bonding aa residues (asn52, tyr 67, and thr78)
are visualized in stick format. Two heme c – protein - connecting residues, cys17
and cys14, are labeled. Based on refi ned crystallographic temperature factors,
the most rigid parts of the molecule are closely associated with the heme group
while surface residues show the greatest fl exibility. In the overall molecule,
90% of the polar atoms participate in hydrogen bonding.
The PDB: 1YCC refi ned model includes 116 water molecules, most of them
in hydrogen - bonding networks near the protein ’ s surface. Mostly hydrophobic
residues surround the heme crevice; however, at least three important water
molecules — wat121, wat166, and wat168 — form hydrogen - bonds with the pro-
pionate oxygen atoms and polar atoms of nearby aa residues. Wat166 is almost