BIOINORGANIC CHEMISTRY A Short Course Second Edition

(lu) #1

70 BIOCHEMISTRY FUNDAMENTALS


Figure 2.23 (A) Amino acid sequence and secondary structure of Zif1, Zif2, and Zif3
zinc fi ngers of Zif268. (B) Base contacts of the − 1, 1, 2, 3, 5, 6 α - helical amino acid resi-
dues of Zif1, Zif2, and Zif3. (C) DNA sequence of the TATA box strand for which zinc
fi ngers were designed. (Figures adapted with permission from Figure 1 of reference 37.
Copyright 1997, American Association for the Advancement of Science.)


Finger 1 MERPYACPVESCDRRFS E L HIRIHTGQK

Finger 2 L HIRTHTGEK

Finger 3 PFACDI-----CGRKFA E HTKIHLRQKD

antiparallelβ sheet region
α helical region
randomized positions
bold letters zinc ion ligands
bold numbers α helix residues interacting with
bases on DNA strands

Finger 1 Finger 2 Finger 3

3'T G C G G G T G C G 5'


5'A C G C C C A C G C 3'


-1 1 2 3 5 6 -1 1 2 3 5 6
R S D E T R

-1 1 2 3 5 6
R S D E K R

TATA 3' G A A A A T A T C G G5'


finger amino acid contacts within the
DNA subsite (note finger 2 D to C
contact outside subsite)

less favorable contacts from position 2
(also outside the finger's DNA subsite)

randomized fingers were selected to bind
at boxed subsites

T T T T A T A G C


-1 1 2 3 5 6
RDSTR

RDSHTT

RDSRRK

A

B C

PFQCRI-----CMRNFS

R S D H T T

a recognition code for zinc - fi nger binding to DNA. One example of such a
system — in this case the so - called Tramtrack (TTK) transcriptional regulator
from theDrosophilia development gene fushi - tarazu — is shown in Figure
2.24.^38 The TTK structural data are deposited as 2DRP in the protein data
bank (PDB).
Two identical zinc - fi nger – protein – DNA double strand interactions are
found in the 2DRP crystal ’ s unit cell. A close - up view of one of these protein –
DNA interactions is visualized in Figure 2.24. A description of the protein –

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