Summary: Eukaryotic DNA topoisomerase I, catalytic core
Eukaryotic DNA topoisomerase I, catalytic core Provide feedback
Topoisomerase I promotes the relaxation of DNA superhelical tension by introducing a transient single-stranded break in duplex DNA and are vital for the processes of replication, transcription, and recombination .
Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG; , Science 1998;279:1504-1513.: Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. PUBMED:9488644 EPMC:9488644
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This tab holds annotation information from the InterPro database.
InterPro entry IPR013500
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [PUBMED:7770916]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [PUBMED:12042765, PUBMED:11395412]. DNA topoisomerases are divided into two classes: type I enzymes (EC; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (EC; topoisomerases II, IV and VI) break double-strand DNA [PUBMED:12596227].
Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA.
This entry represents the catalytic core of eukaryotic and viral topoisomerase I (type IB) enzymes, which occurs near the C-terminal region of the protein.
Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity [PUBMED:1849260]. The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps" around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [PUBMED:9488644].
Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. The crystal structure of an amino-terminal fragment of vaccinia virus DNA topoisomerase I shows that the fragment forms a five-stranded, antiparallel beta-sheet with two short alpha-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure [PUBMED:7994576].
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|Molecular function||DNA binding (GO:0003677)|
|DNA topoisomerase type II (ATP-hydrolyzing) activity (GO:0003918)|
|Biological process||DNA topological change (GO:0006265)|
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|Seed source:||Pfam-B_1377 (release 3.0)|
|Author:||Finn RD, Bateman A, Griffiths-Jones SR|
|Number in seed:||117|
|Number in full:||2875|
|Average length of the domain:||199.50 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||44.73 %|
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build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||16|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Topoisom_I domain has been found. There are 23 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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