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29 a.a.
_ZN
Key reference
Full text Protein Sci 2:951-965 (1993) PubMed id: 8318900
Structures of DNA-binding mutant zinc finger domains: implications for DNA binding. R.C.Hoffman, S.J.Horvath, R.E.Klevit. ABSTRACT
Studies of Cys2-His2 zinc finger domains have revealed that the structures of individual finger domains in solution determined by NMR spectroscopy are strikingly similar to the structure of fingers bound to DNA determined by X-ray diffraction. Therefore, detailed structural analyses of single finger domains that contain amino acid substitutions known to affect DNA binding in the whole protein can yield information concerning the structural ramifications of such mutations. We have used this approach to study two mutants in the N-terminal finger domain of ADR1, a yeast transcription factor that contains two Cys2-His2 zinc finger sequences spanning residues 102-159. Two point mutants at position 118 in the N-terminal zinc finger (ADR1b: 102-130) that adversely affect the DNA-binding activity of ADR1 have previously been identified: H118A and H118Y. The structures of wild-type ADR1b and the two mutant zinc finger domains were determined using two-dimensional nuclear magnetic resonance spectroscopy and distance geometry and were refined using a complete relaxation matrix method approach (REPENT) to improve agreement between the models and the nuclear Overhauser effect spectroscopy data from which they were generated. The molecular architecture of the refined wild-type ADR1b domain is presented in detail. Comparisons of wild-type ADR1b and the two mutants revealed that neither mutation causes a significant structural perturbation. The structures indicate that the DNA binding properties of the His 118 mutants are dependent on the identity of the side chain at position 118, which has been postulated to make a direct DNA contact in the wild-type ADR1 protein. The results suggest that the identity of the side chain at the middle DNA contact position in Cys2-His2 zinc fingers may be changed with impunity regarding the domain structure and can affect the affinity of the protein-DNA interaction.
Literature references that cite this PDB file's key reference
PubMed id Reference
12778114 S.J.Freedman, Z.Y.Sun, A.L.Kung, D.S.France, G.Wagner, and M.J.Eck (2003).
Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2.Nat Struct Biol, 10, 504-512.
PDB code: 1p4q 9300483 M.Schmiedeskamp, P.Rajagopal, and R.E.Klevit (1997).
NMR chemical shift perturbation mapping of DNA binding by a zinc-finger domain from the yeast transcription factor ADR1.Protein Sci, 6, 1835-1848.
9369471 M.Schmiedeskamp, and R.E.Klevit (1997).
Paramagnetic cobalt as a probe of the orientation of an accessory DNA-binding region of the yeast ADR1 zinc-finger protein.Biochemistry, 36, 14003-14011.
8608120 T.N.Jaishree, V.Ramakrishnan, and S.W.White (1996).
Solution structure of prokaryotic ribosomal protein S17 by high-resolution NMR spectroscopy.Biochemistry, 35, 2845-2853.
8750235 V.V.Svetlov, and T.G.Cooper (1995).
Review: compilation and characteristics of dedicated transcription factors in Saccharomyces cerevisiae.Yeast, 11, 1439-1484.
8092710 B.E.Bernstein, R.C.Hoffman, and R.E.Klevit (1994).
Sequence-specific DNA recognition by Cys2, His2 zinc fingers.Ann N Y Acad Sci, 726, 92. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.
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