Crystal structure of a pentamidine-oligonucleotide complex: implications for DNA-binding properties

K J Edwards; T C Jenkins; S Neidle

doi:10.1021/bi00146a011

Crystal structure of a pentamidine-oligonucleotide complex: implications for DNA-binding properties

Biochemistry. 1992 Aug 11;31(31):7104-9. doi: 10.1021/bi00146a011.

Authors

K J Edwards¹, T C Jenkins, S Neidle

Affiliation

¹ Cancer Research Campaign Biomolecular Structure Unit, Institute of Cancer Research, Sutton, Surrey, U.K.

PMID: 1643044
DOI: 10.1021/bi00146a011

Abstract

The crystal structure of the complex formed between the dodecanucleotide d(CGCGAATTCGCG)2 and the drug pentamidine, which is active against the Pneumocystis carinii pathogen in AIDS patients, has been determined to a resolution of 2.1 A and an R-factor of 19.4%. Analysis of the structure has shown the drug to be bound in the 5'-AATT minor groove region of the duplex, with the amidinium groups H-bonded to adenine N3 atoms in an interstrand manner. The drug molecule adopts an extended conformation, and the immediate binding site spans four base pairs. Structural details of the drug-DNA interactions are discussed, and comparison is made with the dodecamer complex of the structurally similar berenil ligand.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
DNA / metabolism*
Molecular Sequence Data
Oligonucleotides / chemistry*
Oligonucleotides / metabolism
Pentamidine / chemistry*
Pentamidine / metabolism
X-Ray Diffraction

Substances

Oligonucleotides
Pentamidine
DNA