Chemistry Reference
In-Depth Information
porphyrin. The two sites, occupied respectively by a Zn
2
þ
ion and a fully hydrated Mg
2
þ
ion, are ~7
˚
apart. Two
of the ligands to the Zn
2
þ
ion in the outer site, His183 and Glu264, are invariant in all ferrochelatases. The side
chains of Glu272, Asp268, and Glu272 are aligned along the
p
-helix, in a line connecting the two metal sites.
Only a
-helix can provide such an alignment of side chains. This is reminiscent of several other metalloproteins,
like nitrogenase and the ferritin superfamily, in which residues in
p
p
-helices function to coordinate metal ions
involved in enzymatic activity.
An interesting question is why does a particular chelatase introduce just one particular divalent transition metal
ion rather than any one of a number of others? It might be because that particular M
2
þ
is present in that biological
compartment (e.g., in the case of haem synthesis, Fe
2
þ
) and present at much larger concentrations than any other.
Clues have begun to appear, however, from experiments in which site-directed mutagenesis of specific amino acid
residues in the proposed metal-ion-binding site of the chelatase has changed the specificity of the metal ion, which
is inserted into the porphyrin.
IRON
e
SULFUR CLUSTER FORMATION
Numerous Fe/S proteins are known in each of the three kingdoms of living organisms, i.e., in Eubacteria,
Archaebacteria, and Eukaryotes, and their multiple functions in electron transport and catalysis are reviewed in
Chapter 13. In contrast to most other cofactors, Fe/S clusters are essentially inorganic in nature, consisting simply
of iron cations (Fe
2
þ
or Fe
3
þ
) and inorganic sulfide anions (S
2
). Our understanding of the way in which these
clusters are assembled has evolved rapidly in the last few years and we summarise our current understanding of the
eukaryotic mitochondrial iron
sulfur cluster (ISC) assembly machinery here. The mitochondrial ISC assembly
system is strikingly similar to that in bacteria, and it is now clear that mitochondria play a prime role in Fe/S
protein biogenesis, since they are not only responsible for maturation of Fe/S proteins inside but also outside of the
organelle. The current view of Fe/S protein biogenesis in eukaryotes (
Fig. 4.11
)
involves the interplay of three
complex multiprotein systems, referred to as ISC assembly, ISC export, and CIA (cytosolic iron
e
sulfur protein
e
assembly machinery).
FIGURE 4.11
A current working model of Fe/S protein biogenesis in eukaryotes. Fe/S protein biogenesis is a complex process involving
three different machineries. The figure depicts the names used for human components, yet in many parts builds on the mechanisms derived from
functional studies in yeast.
(From
Sheftel, Stehling, & Lill, 2010
.
Copyright 2010, with permission from Elsevier.)
