Summary

Eukaryotic DNA topoisomerase I, catalytic core

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 [2].

Literature references

Roca J; , Trends Biochem Sci 1995;20:156-160.: The mechanisms of DNA topoisomerases. PUBMED:7770916
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

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. 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 (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (; 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.

More information about this protein can be found at Protein of the Month: DNA Topoisomerase PUBMED:.

Clan

This family is a member of clan DNA-mend (CL0382), which contains the following 4 members:

DUF3435 Flp_C Phage_integrase Topoisom_I

Gene Ontology

Cellular component	chromosome (GO:0005694)
Molecular function	DNA binding (GO:0003677)
Molecular function	DNA topoisomerase (ATP-hydrolyzing) activity (GO:0003918)
Biological process	DNA topological change (GO:0006265)

External database links

HOMSTRAD:	Topoisomerase_I_core
PANDIT:	PF01028
PROSITE:	PDOC00159
SCOP:	1a31 1a36
SYSTERS:	Topoisom_I

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

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Alignment:	Seed (137) Full (503) NCBI (729) Metagenomics (170)
Viewer:

Formatting options

Alignment:	Seed (137) Full (503)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (137) Full (503) NCBI (729) Metagenomics (170)
Full length sequences	Full-sequences (503)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Pfam-B_1377 (release 3.0)

Previous IDs:

Topoisomerase_I;

Type:

Domain

Author:

Finn RD, Bateman A, Griffiths-Jones SR

Number in seed:

137

Number in full:

503

Average length of the domain:

225.60 aa

Average identity of full alignment:

31 %

Average coverage of the sequence by the domain:

45.45 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.9	20.9
Trusted cut-off	27.0	23.0
Noise cut-off	20.2	19.8

Model length:

235

Family (HMM) version:

13

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD 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.

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Family: Topoisom_I (PF01028)

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