PDBsum entry 195d

DNA

PDB id

195d

Contents

			DNA/RNA

			Ligands

					_NT

			Waters ×87

References listed in PDB file

Key reference

Title

X-Ray structures of the b-Dna dodecamer d(cgcgttaacgcg) with an inverted central tetranucleotide and its netropsin complex.

Authors

K.Balendiran, S.T.Rao, C.Y.Sekharudu, G.Zon, M.Sundaralingam.

Ref.

Acta Crystallogr D Biol Crystallogr, 1995, 51, 190-198. [DOI no: 10.1107/S0907444994010759]

PubMed id

15299320

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.

Abstract

The crystal structures of the B-DNA dodecamer d(CGCGTTAACGCG) duplex (T2A2), with the inverted tetranucleotide core from the duplex d(CGCGAATTCGCG) [A2T2, Dickerson & Drew (1981). J. Mol. Biol. 149, 761-768], and its netropsin complex (T2A2-N) have been determined at 2.3 A resolution. The crystals are orthorhombic, space group P2(1)2(1)2(1), unit-cell dimensions of a = 25.7, b = 40.5 and c = 67.0 A, for T2A2 and a = 25.49, b = 40.87, c = 67.02 A for T2A2-N and are isomorphous with A2T2. The native T2A2 structure, with 70 water molecules had a final R value of 0.15 for 1522 reflections (F > 2sigma), while for the netropsin complex, with 87 water molecules, the R value was 0.16 for 2420 reflections. In T2A2, a discontinuous string of zig-zagging water molecules hydrate the narrow A.T minor groove. In T2A2-N, netropsin binds in one orientation in the minor groove, covering the TTAA central region, by displacing the string of waters, forming the majority of hydrogen bonds with DNA atoms in one strand, and causing very little perturbation of the native structure. The helical twist angle in T2A2 is largest at the duplex center, corresponding to the cleavage site by the restriction enzymes HpaI and HincII. The sequence inversion AATT-->TTAA of the tetranucleotide at the center of the molecule results in a different path for the local helix axis in T2A2 and A2T2 but the overall bending is similar in both cases.



	Figure 1. Fig. 1. Electron density in omit 2Fo -Fc maps using minimum bias coefficients (Read, 1986) in the native T2A2 (top) and the netropsin complex (bottom). View is into the the minor groove. The contours are drawn at 1.2o. Waters in the native structure spanning the netropsin-binding region and netropsin atoms in the complex, respectively, were omitted from the phasing. The atomic model of netropsin after refinement is superposed. Notice the discrete electron density in the native for the water moicules bound in the mirror groove and the continuous electron density in the complex for netropsin with characteristic bulges corresponding to the C~---O and N--CH3 groups of the drug.		Figure 5. Fig. 5. Base-stacking interactions in T2A2 (left) and A2T2 (fight) at steps where the step types (Py/Pu) have changed: (a) 4-5, (b) 6-7 and (c) 8-9. Dark bonds for the base pair on the top and open bonds for the base at the bottom. Notice the lack of stacking at the central Py- Py step 6-7 in T2A2, which is overwound (see text).

	Headers