Chemistry Reference
In-Depth Information
Chapter 4
Biological Ligands for Metal Ions
Introduction
69
Insertion of Metal Ions into Metalloproteins
76
Chelatase
e
The Terminal Step in Tetrapyrrole Metallation
77
Iron
e
Sulfur Cluster Formation
79
More Complex Cofactors
e
MoCo, FeMoCo, P-clusters, H-clusters, and CuZ
80
Siderophores
86
INTRODUCTION
In Chapter 2, we explained the basic notions involved in the coordination chemistry of metal ions. We now
consider potential ligands, which could be involved in binding metals in metalloproteins. We already defined
ligand binding as the affinity of the metal ion for any atom, group, or molecule that is attached to the central metal
ion. We can divide them into three categories:
naturally occurring amino acids in the protein itself, and amino acids within the protein which have been
chemically modified:
l
low-molecular-weight inorganic anions
l
organic cofactors
l
As was pointed out in Chapter 2, biologically important metal ions and their ligands can be classified
according to the hard-soft theory of acids and bases (Table 2.1). While there are exceptions, most metal ions
bind to donor ligands as a function of preferences based on this concept, with hard acids (metal ions, like Na
þ
,
K
þ
,Ca
2
þ
,Mg
2
þ
, and Fe
3
þ
) binding preferentially to hard bases (ligands, like O), and soft acids (like Cu
þ
)to
soft bases (like S and N).
Amino Acid Residues
Of the 20 amino acids present in proteins (Chaper 3), only a relatively small number are potential metal ligands.
The ligand groups, which are encountered most often are the thiolate of Cys, the imidazole of His, the carboxylates
of Glu and Asp, and the phenolate of Tyr (
Fig. 4.1
)
. Less frequently, we encounter the thioether group of Met, the
amino group of Lys and the guanidino group of Arg, and the amide groups of Asn and Gln. Metal ions can also
bind to peptide bonds, through the carbonyl or the deprotonated amide nitrogen, and to the terminal amino and
carboxyl groups of the protein.
Cysteine can bind to either one or two metal ions, and is frequently found as a ligand to iron (e.g., in
S clusters) and to Cu
þ
(e.g., in copper chaperones which transfer copper to specific copper-binding
proteins). Histidine can bind metal ions in two positions, and has a strong preference for Cu
2
þ
.The
Fe
e
