BIOINORGANIC CHEMISTRY A Short Course Second Edition

64 BIOCHEMISTRY FUNDAMENTALS

zinc - fi ngers, that interact with DNA.^24 Zinc ions are required for correct
protein folding into its tertiary structure and required for specifi c DNA inter-
actions, although the Zn(II) ions themselves do not interact directly with the
DNA strands. Since its sequence has become available, researchers have
attempted to fi nd the most common protein domains encoded within the
human genome. The cys 2 his 2 zinc - fi nger protein domain has been identifi ed as
one of the most common and recognizable; in 2004, more than 4000 such
domains had been found in over 700 proteins.
Further research has led to a classifi cation of zinc - fi nger proteins to include
various criteria: (1) one or multiple repeat units of about 30 amino acids per
fi nger; (2) both two cys and two his (cys 2 his 2 ) with their spacing conserved (the
same amino acids occurring in the same locations in many different biological
species); (3) two aromatic residues, usually phenylalanine (F), and tryrosine
(Y), and the hydrophobic aa leucine (L) conserved in the TFIIIA repeat units;
(4) a three - dimensional structure of the sequence that resembles a fi nger (see
Figure 2.20 ).^25 Comparisons with metalloproteins of known structure have
allowed the development of a detailed three - dimensional model for these
domains consisting of two antiparallelβ - sheets followed by an α - helix (see
Figure 2.21 ). The proposed structure provides a basis for understanding the
detailed roles of the conserved residues and allows construction of a model
for the interaction of these proteins with nucleic acids in which the proteins
wrap around the nucleic acids in the major groove.^26 Usually, zinc - fi nger pro-
teins play a regulatory function and are found in nucleic acid polymerases and
transcription factors. The role of zinc ion is not catalytic but structural, main-
taining the structure of proteins that bind to DNA to activate and deactivate
genes.
The consensus aa sequence for zinc - fi nger repeats, commonly called cys 2 his 2
type zinc - fi ngers, is often (phe, tyr) - X - cys - (X) 2 - 5 - cys - (X) 3 - phe - (X) 5 - leu or other
hydrophobic residue - (X) 2 - his - (X) 3 - 5 - his - (X) 5 , where X is any amino acid.^27 The
residues in bold type indicate amino acids ligands involved in zinc ion binding.

Figure 2.20 Schematic representation of a zinc - fi nger domain from TFIIIA and
related proteins. X represents any amino acid, and conserved amino acids are histidine
(H), cysteine (C), tyrosine (Y), phenylalanine (F), and leucine (L).

C H

C H

C

L

Helical

portion

Zn

X

X

X

X

X

X

N Y XX

XX

X

X

X

X

X

XX

X

X

X

F X