in RNA, which will in turn affect contacts between the zinc - fi nger proteins and
the nucleic acids. While the binding of Sp1 to its preferred DNA – DNA and
DNA – RNA segments was similar, ZF - QQR not only bound more tightly to
its preferred DNA – DNA segments than Sp1 but bound DNA – RNA segments
fi ve times more strongly than the DNA – DNA segments. Both Sp1 and ZF -
QQR proteins bound much less well to RNA - DNA hybrids. The authors found
that interactions between the zinc - fi nger proteins and the DNA – RNA hybrids
were dependent on which strand was RNA (DNA – RNA preferred over
RNA – DNA by both Sp1 and ZF - QQR proteins) and were sequence - specifi c
as well. It is also important to realize that although DNA – RNA hybrids are
not well understood, it is known that they do adopt structures that are inter-
mediate between A - and B - form DNA. The authors concluded that interac-
tions with DNA – RNA hybrids should be considered with regard to the
biological roles of zinc - fi nger proteins because these proteins could be designed
to target specifi c DNA – RNA hybrid structures in vivo.
In conclusion, research on zinc - fi nger – DNA interactions has indicated that
secondary structure of the zinc - fi nger proteins as well as their primary amino
acid residue sequences are important in designing proteins to interact with
specifi c DNAs. The points of DNA contact appear to be principally on one
strand of dsDNA and, for many but certainly not all interactions, occur at
guanine bases. Although early research suggested that the zinc - fi nger protein –
DNA interactions would be readily characterized, copied, and applied to new
systems through application of a “ recognition code, ” the situation now appears
to be more complex than originally thought. Progress continues on research
that will hopefully lead to advances in zinc - fi nger – DNA interactions along
with the capability to use this knowledge to good effect in gene therapeutic
and other medicinal applications. The latest review information on DNA rec-
ognition by cys 2 his 2 zinc - fi nger proteins at the time of this book was contained
in the articles of reference 34.
2.5 Summary and Conclusions,
The material introduced in this chapter was chosen to refl ect the emphasis of
information presented in the rest of this short text. In Chapter 3 , more infor-
mation on the X - ray crystallographic and NMR solution structural techniques
applied to proteins and nucleic acids will be presented. Analysis of metallo-
proteins and metalloenzymes discussed in Chapters 5 , 6, and 7 provides impor-
tant information not only on structures but on functions of these bioinorganic
systems. Knowledge of the protein composition and structural analyses of
these metalloproteins and metalloenzymes will be assumed on the reader ’ s
part from the background presented in this chapter and the next. The student
is invited to refer to Chapter 2 materials often for greater understanding of
the bioinorganic systems presented in the following chapters.
SUMMARY AND CONCLUSIONS 73
