BIOINORGANIC CHEMISTRY A Short Course Second Edition

CYTOCHROMES c 409

In addition to the four porphyrin nitrogen ligands, cytochrome c ’ s heme
iron ion carries one axial histidine ligand. Some variety exists for the iron ion ’ s
second axial ligand, although it is often the S δ atom of a methionine residue.
In an early classifi cation study, Ambler identifi ed four classes of cytochromes
c depending on the number of hemes, the type and position of the axial iron
ligands, and the redox potential.^27 More information about cytochromes c can
be found in a 1996 book written by Scott and Mauk.^100 Recently, Bertini et al.
have published an extensive study of cytochromes c that broadly corresponds
to those of Ambler ’ s class I cytochromes.^101 These cytochromes feature a
single - heme domain and possess a “ cytochrome c fold. ” This particular fold
has been well described in the literature^100 and can be identifi ed as a superfam-
ily in protein classifi cation tools such as CATH^102 ( http://www.cathdb.info/
latest/index.html ) or SCOP^103 ( http://scop.mrc - lmb.cam.ac.uk/scop/ ). The
CATH database classifi es protein structures in the Protein Data Bank (PDB)
in a hierarchical manner. Crystal structures resolved to better than 3.0 Å and
NMR structures are classifi ed. CATH has four major levels of hierarchy: (1)
C lass (mainly alpha ( α - helical), mainly beta ( β - pleated sheet), alpha - beta, few
secondary structures; (2) A rchitecture (overall shape; e.g., alpha four - helical
bundle as in cytochrome c); (3) T opology (fold family, determined by overall
shape and connectivity of the protein secondary structure); and (4) H omolo-
gous superfamily (groups together protein domains thought to share a common
ancestor and are therefore homologous). The SCOP (Structural Classifi cation
of Proteins) database provides a comprehensive description of structural and

Figure 7.32 (A) Cytochrome c heme Fischer numbering system. (Adapted with per-
mission from Figure 1 of reference 119b .) Copyright 2000 National Academy of Sci-
ences, U.S.A.) (B) The protoheme IX numbering system as outlined in reference 112.

A D

B C

N N

N N

Fe

C

• O O
  C


• O O

S

1 S

2 3

4

5

7 6

8

α

β

γ

δ

cys17

cys14

Structure of c-type heme group with Fischer nomenclature.
Thioether linkages to protein chain at positions 2 and 4.
Propionate groups at positions 6 and 7.

A

B C

CHC

C1C

C2C

C3C

CBC

NB NC C4C

ND

CHD

CMC

CHB

CBD

O1D O2D

D

N N

N N

Fe

C

O O

C

O-O -

CGA CGD

AB

CHA

CAC

NA

CAA CBA CAD

O1A O2A