1k18
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Minimized Average NMR Structure of the Zinc Finger Domain of Human DNA Polymerase-alpha
OverviewOverview
The carboxy terminus of the human DNA polymerase-alpha contains a zinc, finger motif. Three-dimensional structures of this motif containing 38, amino acid residues, W L I C E E P T C R N R T R H L P L Q F S R T G P L C, P A C M K A T L Q P E, were determined by nuclear magnetic resonance (NMR), spectroscopy. The structures reveal an alpha-helix-like domain at the, amino terminus, extending 13 residues from L2 through H15 with an, interruption at the sixth residue. The helix region is followed by three, turns (H15-L18, T23-L26 and L26-A29), all of which involve proline. The, first turn appears to be type III, judging by the dihedral angles. The, second and third turns appear to be atypical. A second, shorter helix is, formed at the carboxy terminus extending from C30 through L35. A fourth, type III turn starting at L35 was also observed in the structure. Proline, serves as the third residue of all the turns. Four cysteine residues, two, located at the beginning of the helix at the N-terminus and two at the, carboxy end, are coordinated to Zn(II), facilitating the formation of a, loop. One of the cysteines at the carboxy terminus is part of the atypical, turn, while the other is the part of the short helix. These structural, features are consistent with the circular dichroism (CD) measurements, which indicate the presence of 45% helix, 11% beta turns and 19%, non-ordered secondary structures. The zinc finger motif described here is, different from those observed for C(4), C(2)H(2), and C(2)HC modules, reported in the literature. In particular, polymerase-alpha structures, exhibit helix-turn-helix motif while most zinc finger proteins show, anti-parallel sheet and helix. Several residues capable of binding DNA, T, R, N, and H are located in the helical region. These structural features, imply that the zinc finger motif is most likely involved in binding DNA, prior to replication, presumably through the helical region. These results, are discussed in the context of other eukaryotic and prokaryotic DNA, polymerases belonging to the polymerase B family.
DiseaseDisease
Known disease associated with this structure: N syndrome, 310465 (1) OMIM:[312040]
About this StructureAbout this Structure
1K18 is a Single protein structure of sequence from [1]. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.
ReferenceReference
Nuclear magnetic resonance structures of the zinc finger domain of human DNA polymerase-alpha., Evanics F, Maurmann L, Yang WW, Bose RN, Biochim Biophys Acta. 2003 Sep 23;1651(1-2):163-71. PMID:14499601
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