BIOINORGANIC CHEMISTRY A Short Course Second Edition

350 IRON-CONTAINING PROTEINS AND ENZYMES

studies confi rmed by many other instrumental and analytical techniques, a
clear picture of the metalloprotein ’ s active site has emerged.
The active site of hemoglobin and myoglobin consists of an iron(II)
protoporphyrin IX (the heme shown in Figure 7.1 ) encapsulated in a water -
resistant pocket and bound to the protein through a single coordinate bond
between the imidazole nitrogen of the proximal histidine residue (His93, F8
for myoglobin) and the iron(II) (see Figure 7.4 ). The proximal Fe – N bond
vector has an approximate 10 ° tilt off the heme normal. Additionally, other
protein residues such as the leucine, isoleucine, valine, and phenylalanine
interact with the heme, holding it in place through hydrophobic interactions.
The fi ve - coordinate Fe(II) can add dioxygen in its sixth, vacant coordination
site, and a variety of other small ligands (CO, NO, RCN) may also bind there.
Other amino acid residues that control the immediate environment with
respect to polar, hydrophobic, or steric interactions surround the distal, vacant
coordination site of the deoxy form. When O 2 is bound, it is stabilized by
hydrogen - bond interactions through the distal histidine (his64, E7). See Figure
7.4. The H - bond interactions may affect O 2 affi nity and inhibit pathways
leading to further oxidation and μ - oxo dimer formation (see Section 7.2.6 and
Figure 7.8 ).^9 The distal histidine hydrogen bonding structure for hemoprotein
and for a model “ amide basket handle ” heme is illustrated in Figure 7.7.
Despite the many model compounds that have been prepared, picket
fence porphyrin and its many cogeners, fi rst reported by the Collman research
group in 1974,^13 remains the only porphyrin - type ligand system yielding

Figure 7.7 Distal histidine hydrogen bonding structure for hemoglobin (left) and a
heme model (right). (Reprinted with permission from Figure 12 of reference 9. Copy-
right 1994, American Chemical Society.)

N

“proximal” histidine

Heme group in hemoglobin Model compound

“distal” histidine

NFe

O O O

O

NH

O=C

C=O

O

HN

N

N

NFe

N

N

HN

N

CNH

C

O

=

H

N

N

N

N

N

MN