DSSR-PyMOL cartoon-block schematics: PDB entry 303d

PDB-id

303d; DSSR-derived features in text and JSON formats

Class

DNA

Method

X-ray (2.2 Å)

Summary

Meta-hydroxy analogue of hoechst 33258 ('hydroxyl out' conformation) bound to d(cgcgaattcgcg)2

Reference

Clark GR, Squire CJ, Gray EJ, Leupin W, Neidle S (1996): "Designer DNA-binding drugs: the crystal structure of a meta-hydroxy analogue of Hoechst 33258 bound to d(CGCGAATTCGCG)2." Nucleic Acids Res., 24, 4882-4889. doi: 10.1093/nar/24.24.4882.

Abstract

An analogue of the DNA binding compound Hoechst 33258, which has the para hydroxyl group altered to be at the meta position, together with the replacement of one benzimidazole group by pyridylimidazole, has been cocrystallized with the dodecanucleotide sequence d(CGCGAATTCGCG)2. The X-ray structure has been determined at 2.2 A resolution and refined to an R factor of 20.1%. The ligand binds in the minor groove at the sequence 5'-AATTC with the bulky piperazine group extending over the CxG base pair. This binding is stabilised by hydrogen bonding and numerous close van der Waals contacts to the surface of the groove walls. The meta-hydroxyl group was found in two distinct orientations, neither of which participates in direct hydrogen bonds to the exocyclic amino group of a guanine base. The conformation of the drug differs from that found previously in other X-ray structures of Hoechst 33258-DNA complexes. There is significant variation between the minor groove widths in the complexes of Hoechst 33258 and the meta-hydroxyl derivative as a result of these conformational differences. Reasons are discussed for the inability of this derivative to actively recognise guanine.