Chemistry Reference
In-Depth Information
hydroxide and Asp ligands. It is postulated that the iron centre has a terminal hydroxide ligand, whereas the zinc
has an aqua ligand. We do not discuss the mechanism here, but it must be different from the alkaline phosphatase
because the reaction proceeds with inversion of configuration at phosphorus (
Figure 12.18
)
.
OH
OH
2
O
His-N
N-His
NH
2
Fe
Zn
Tyr-O
Asp
O
O
O
N-His
Asn
O
Asp
FIGURE 12.18
Coordination of the dinuclear site in kidney bean purple acid phosphatase.
(Adapted from
Parkin, 2004
.)
ZINC FINGERS DNA- AND RNA-BINDING MOTIFS
Aaron Klug discovered the first of the eukaryotic DNA-binding motifs in Xenopus transcription factor IIIA
(TFIIIA), a protein which binds to the 5S rRNA gene. The resulting complex subsequently binds two other
transcription factors and RNA polymerase III, which leads to the initiation of transcription of the 5S rRNA
gene. The TFIIIA molecule contains 9 similar ~30-residue-long, tandemly repeated modules. Each of these
modules contains two invariant Cys residues, two invariant His residues, and several conserved hydrophobic
residues (
Figure 12.19
), and a Zn
2
þ
ion, which is tetrahedrally coordinated by the invariant Cys and His
(Left) Schematic representation of tandemly repeated zinc finger motif with their tetrahedrally coordinated Zn
2
þ
ions.
Conserved amino acids are labeled and the most probable DNA-binding side chains are indicated by balls. (Right) A ribbon diagram of a single
zinc finger motif in a ribbon diagram representation.
FIGURE 12.19
(From Voet & Voet, 2004. Copyright 2004 with permission from John Wiley and Sons.)
residues. These so-called Cys
2
e
each in a family of eukaryotic transcription factors. In some zinc fingers, the invariant His residues are
replaced by Cys residues (Cys
2
e
Cys
2
Zinc Fingers), while in others six Cys residues bind two Zn
2
þ
ions
(Dinuclear Cys
6
Zinc Fingers). Structural diversity is a hallmark of zinc finger proteins, and it appears that the
