[Computer analysis of conformational and physicochemical percularities of sequences cleaved by DNA topoisomerase I].
After complexation of DNA with enzymes a specific adaptation of DNA structure including its partial or nearly complet melting, change of sugar-phosphate backbone structure, stretching, compression, bending or kinking, flipping out of nucleotides from the DNA helix, etc. take place. The full set of such changes is specific for each individual enzyme and is a very important for effective adjustment of reacting orbitals of enzyme and specific DNA atoms with accuracy up to 10-15 degrees. Efficiency of DNA sequence adaptation in the direction providing by enzyme depends on many specific structural characteristics of DNA. Maximal adjustment of DNA structure can be achieved only for specific sequences, therefore on going from nonspecific to specific DNAs the increase of the catalytic rate by 4-8 orders of magnitude takes place. DNA topoisomerase I is a sequence-dependent enzyme, but it can cleave with lower efficiency DNA sequences, which are significantly different from an optimal one. We have carried out the computer analysis of structural characteristics of many DNA sequences utilizing by topoisomerase using the method which is based on the analysis of conformational and physico-chemical characteristics of DNA helix and gives a detailed information about similarities or differences of DNA structural units. In addition to such characteristics as base tilt angle, shift of base pair, helix steering angle, and helix step for all cleaved sequences the presence of sterically disadvantageous contacts in small grove between N3 and NH2 of guanines and N3 of adenines were detected which corresponds to the presence Py-Pu dinucleotides in the cleavaged site. In addition, for optimal sequences bending of DNA helix toward major groove is characterized. The proposed method seems to be a very perspective for the analysis of an efficiency of nucleic acids cleavage by different DNA- and RNA-dependent enzymes.
D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D004247:DNA / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D006801:Humans; D009690:Nucleic Acid Conformation
D004247:DNA; D004264:DNA Topoisomerases, Type I