C-terminal domains of Escherichia coli topoisomerase I belong to the zinc-ribbon superfamily.
Detection of remote evolutionary connections is increasingly difficult with sequence and structural divergence. A combination of sequence and structural analysis, in which statistically supported sequence similarity had a crucial impact, revealed that Escherichia coli topoisomerase I C-terminal fragment is evolutionarily related to the three tetracysteine zinc-binding domains of the enzyme. Spatial structure analysis of this C-terminal fragment indicates that it consists of two structurally similar domains and suggests homology between them. Sequence similarity between the zinc-binding domains of type Ia topoisomerases and transcription regulators of known spatial structure helps to conclude that E. coli topo I contains five copies of a zinc ribbon domain at the C terminus. Two of these domains, corresponding to the C-terminal fragment, lost their cysteine residues and are probably not able to bind zinc. Present analyses lead to the classification of the C-terminal fragment of E. coli topoisomerase I as a member of zinc ribbon superfamily, despite the absence of zinc-binding sites.
Grishin
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Biochemistry Department, University of Texas Southwestern Medical Center, 5323, Harry Hines Blvd, Dallas, TX, 75390-9038, USA. grishin@chop.swmed.edu
D000595:Amino Acid Sequence; D001665:Binding Sites; D003545:Cysteine / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D010446:Peptide Fragments; D014157:Transcription Factors; D004264:DNA Topoisomerases, Type I; D015032:Zinc; D003545:Cysteine