Protein-nucleotide interactions in E. coli DNA topoisomerase I.
DNA topoisomerases are the enzymes responsible for controlling and maintaining the topological states of DNA. Type IA enzymes work by transiently breaking the phosphodiester backbone of one strand to allow passage of another strand through the break. The protein has to perform complex rearrangements of the DNA, and hence it is likely that different regions of the enzyme bind DNA with different affinities. In order to identify some of the DNA binding sites in the protein, we have solved the structures of several complexes of the 67 kDa N-terminal fragment of Escherichia coli DNA topoisomerase I with mono- and trinucleotides. There are five different binding sites in the complexes, one of which is adjacent to the active site. Two other sites are in the central hole of the protein and may represent general DNA binding regions. The positions of these sites allow us to identify different DNA binding regions and to understand their possible roles in the catalytic cycle.
Feinberg
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Department of Biochemistry, Molecular Biology and Cell Biology, Northwerstern University, 2153 Sheridan Road, Evanston, Illinois 60208, USA.
Changela
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Mondragón
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D000244:Adenosine Diphosphate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D004583:Electrons; D004926:Escherichia coli / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009711:Nucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D004268:DNA-Binding Proteins; D009711:Nucleotides; D010446:Peptide Fragments; D010710:Phosphates; D000244:Adenosine Diphosphate; D004247:DNA; D004264:DNA Topoisomerases, Type I