303D

META-HYDROXY ANALOGUE OF HOECHST 33258 ('HYDROXYL OUT' CONFORMATION) BOUND TO D(CGCGAATTCGCG)2

Summary for 303D

• Entry DOI: 10.2210/pdb303d/pdb
• Descriptor: DNA (5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'), 3-[5-[5-(4-METHYL-PIPERAZIN-1-YL)-1H-IMIDAZO[4,5-B]PYRIDIN-2-YL]-BENZIMIDAZOL-2-YL]-PHENOL, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: b-dna, double helix, complexed with drug, dna
• Total number of polymer chains: 2
• Total formula weight: 7776.57

Authors

Clark, G.R.,Squire, C.J.,Gray, E.J.,Leupin, W.,Neidle, S. (deposition date: 1996-06-26, release date: 1997-01-20, Last modification date: 2024-04-03)

Primary citation

Clark, G.R.,Squire, C.J.,Gray, E.J.,Leupin, W.,Neidle, S.
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, 1996

PubMed 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.

PubMed: 9017011
DOI: 10.1093/nar/24.24.4882

Experimental method

X-RAY DIFFRACTION (2.2 Å)