A molecular mechanics study of spermine complexation to DNA: a new model for spermine-poly(dG-dC) binding.

Molecular mechanics calculations of the binding of spermine to a number of solvated DNA helices have led to the development of a new model for spermine complexation. The structural details of the complexes formed with d(GCGCGCGCGC)2 and d(ATATATATAT)2 decamers allowed a rationalization of the observed experimental differences for binding to these two helices. For d(ATATATATAT)2 it was concluded that spermine remains in a cross-major groove binding site. Conversely, for d(GCGCGCGCGC)2 spermine reorientation via specific ligand-base-pair hydrogen-bond formation allows complexation along the major groove. The solvent plays an important role in differentiating the two binding modes. A mechanism of spermine complexation to natural DNA is postulated from these results. Past experimental data are also considered in the context of the new model.     

Methods for discovering novel motifs in nucleic acid sequences

We describe a computer tool to aid the discovery of new motifsin nucleic acid sequences. A typical use would be to analysea set of upstream regions from a family of related genes inorder to find possible control sequences. The heart of the methodis the creation of dictionaries of related subsequences. Thesedictionaries can then be analysed to look for the commonestor best-defined subsequences, those that occur in the highestnumber of different sequences, or for those in equivalent positionswithin the family. We show the application of the method toa set of E. coli promoter sequences. Received on May 9, 1989; accepted on July 27, 1989     

Changes in muscle crossbridges when β,γ-imido-ATP binds to myosin

We have studied the binding of β,γ-imido-adenosine-5′-triphosphate to glycerol-extracted insect flight and rabbit back muscle fibres. The binding was at relatively high affinity, of the same quantity as that of other nucleotides, and was inhibited by the presence of ATP. We concluded that imido-ATP bound, without hydrolysis, at the enzymic site of myosin. The mechanical effects of imido-ATP on the glycerol-extracted fibres were measured: concentrations sufficient to bind to myosin caused a small increase in the length of the rigor muscle for a given tension without alteration in the shape of the length-tension diagram. The magnitude of the length change paralleled the binding curve of imido-ATP to the fibre. We concluded that binding caused some change in myosin without its detachment from actin. Electron microscopy and X-ray diffraction studies of glycerol-extracted flight muscle fibres showed an increase in the angle of attachment of myosin to actin when imido-ATP was added. The results are discussed in relation to current concepts of force generation in active muscle.     

Pulmonary phospholipied biosynthesis and the ability of the fetal rabbit lung to reduce cortisone to cortisol during the final ten days of gestation

Incubation of fetal lung tissue with 0.2 μM ¹⁴C-cortisone revealed a 12-fold increase in the rate of reduction of cortisone to cortisol between day 22 and day 30 of gestation in the rabbit. This increase correlated closely with the increase in the rate of incorporation of ¹⁴C-choline into total lung lipids during the same period. In light of these findings it would seem inadequate to attempt to relate the plasma cortisol concentration alone with the rate of lung maturation. In addition, one would need consider both the plasma concentration of cortisone and the activity of 11β-hydroxysteroid dehydrogenase (11β-HSD) in the lung.