A DNA-porphyrin minor-groove complex at atomic resolution: The structural consequences of porphyrin ruffling

The crystal structure of a B-type DNA hexanucleotide duplex complexed with the porphyrin molecule nickel-[tetra-N-methylpyridyl] porphyrin has been so lved by multiwavelength anomalous diffraction phasing and refined to an R f actor of 11.5% at a resolution of 0.9 Angstrom. The structure has been solv ed and refined as two crystallographically independent duplexes, stacked en d to end. Contrary to expectation, the porphyrin molecule is not intercalat ed into the duplex but is stacked onto the ends of the two-duplex stack. Th e porphyrin molecule is highly buckled as a consequence of the nickel coord ination, which produces large changes in local DNA structure. A second mode of porphyrin binding is apparent as a consequence of crystal packing, whic h places the ligand in the minor groove of an adjacent duplex. This structu re thus provides, to our knowledge, the first atomic visualization of minor -groove binding for a porphyrin molecule. The geometry of groove binding pr ovides a ready explanation for porphyrin-induced DNA strand cleavage at deo xyribose residues.