BIOINORGANIC CHEMISTRY A Short Course Second Edition

(lu) #1

DNA interaction follows as adapted from reference 38. The 2DRP X - ray
crystallographic structure was solved to 2.8 - Å resolution. Two zinc - fi nger
motifs (F1 and F2) form independent DNA - binding modules, each positioned
with the N terminus of the protein ’ s α - helix pointing into the major groove
and making base - specifi c contacts. Most of the protein – DNA contacts are
made on the primary strand of the 18 - base - pair dsDNA, although one contact
in F2 — namely, asp154 ( 2 ) to C32 — connects to the complementary DNA
strand. The bold number shown in parentheses represents the position of the
residue on theα - helix. The aa residue, asp154, and the cytosine base, C32, are
labeled in Figure 2.24. In Figure 2.24 , the DNA strands are shown in black
cartoon form and the protein domain is shown in gray. The specifi c nucleobases
and amino acid residues that contact each other are shown in stick format —
nucleobases in black and amino acids in gray. Notice that all of the contacting
nucleobases are found on one DNA strand — namely, A7, G8, G9, A10, and
T11 — except for one, C32, which is found on the opposing strand. The three
amino acids of zinc - fi nger domain F1 making contact with the primary strand
of DNA are: ser124 ( 2 ) to T11, asn125 ( 3 ) to A10, arg128 ( 6 ) to G9. The bold
numbers in parentheses indicate the position of the aa residue along the DNA -
contacting α - helix. (See Figures 2.23A and 2.23B , where the notations are
shown for a different zinc - fi nger domain.) The two amino acids of F2 making
contact with the primary DNA strand are: arg152 ( − 1 ) to G8 and asn155 ( 3 )
to A7. In F1, the Zn(II) ion (shown in stick form) is coordinated by the N ε 2


Figure 2.24 Amino acid — double - stranded DNA contacts for zinc - fi nger protein
PDB: 2DRP as described in reference 38 and the text. Visualized using The PyMOL
Molecular Graphics System and ChemDraw Ultra, version 10.0. (Printed with permis-
sion of Delano Scientifi c, LLC and CambridgeSoft Corporation.)


C32

asp154

Zn(II)

Zn(II)

A7

T11

domain F2

domain F1

ZINC-FINGER PROTEINS 71

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