DNA Topoisomerase

What InterPro Tells Us

P11387 Human DNA Topoisomerase I

InterPro Domain Architecture

InterPro Entry	Signatures	Graphical Match	Method Name
IPR001631	PF01028		Topoisom_I
IPR001631	PR00416		EUTPISMRASEI
IPR001631	PS00176		TOPOISOMERASE_I_EUK
IPR001631	SM00435		TOPEUc
IPR008336	PF02919		Topoisom_I_N
IPR009054	SSF46596		Topismrse_insert
IPR011010	SSF56349		DNA_brk_join_enz
Structural Features
1k4t	1k4tA
1.10.10.41.1	1a31A1
1.10.132.10.1	1a31A4
1.10.132.10.1	1a35A4
1.10.132.10.1	1k4tA4
2.170.11.10.1	1a31A2
3.90.15.10.1	1a31A3
a.2.8.1	d1k4ta1
d.163.1.2	d1a31a1
d.163.1.2	d1k4ta2
e.15.1.1	d1a31a2

From the graphical match above, you can see that the signatures are grouped into four InterPro entries for human topoisomerase I. These entries give information about the domain architecture of the protein, as well as its family relationships.

To look at the family relationships, we need to consider entry IPR001631, which represents the family of eukaryotic class I DNA topoisomerases, and which has four signatures: PF01028 from the PFAM database, PR00416 from the PRINTS database, PS00176 from the PROSITE database, and SM00435 from the SMART database.

The domain architecture of human DNA topoisomerase I consists of at least three domains, depending upon the classification. The most N-terminal signature represents the DNA-binding domain of eukaryotic DNA topoisomerase I, IPR008336, which has one signature, PF02919 from the PFAM database. The next domain is IPR011010, the catalytic core of DNA-breaking-rejoining enzymes, which is represented by one signature, SSF56349 from the SUPERFAMILY database. This catalytic core domain is found not only in DNA topoisomerase I enzymes, but also in phage integrase and recombinases families of proteins, indicating homology between these protein families for this domain. This domain contains an insert domain, which is only present in eukaryotic DNA topoisomerase I enzymes, but not in the integrase or recombinases catalytic core domains. IPR009054 represents this dispensable insert domain, which has one signature, SSF46596 from the SUPERFAMILY database.

The remaining eleven entries in the table above give information on the structure of this protein, presenting known structural data from the structural database PDB (green stripe) and the structural classification databases CATH (pink stripe) and SCOP (black stripe) (the names such as d1k4ta1 are derived from the PDB entry upon which they are based, here PDB entry 1k4t, chain a, fragment 1). The graphical match for the PDB entry 1k4tA displays the full length of the original PDB entry, here covering all but the N-terminal region of the protein. The CATH and SCOP entries breakdown the PDB data into its constituent domains and provide a structural classification for each, although here their classification schemes differ for one another with respect to both the DNA-binding and the catalytic domains – this can be accounted for by SCOP keeping together regions that make up a single functional unit, while CATH breaks down a protein into each individual structural part: the N-terminal DNA-binding domain (SCOP d1a31a2 classed as a + b; CATH 1a31A1 classed as a, 1a31A2 classed as b), the catalytic core (SCOP d1a31a1 and d1k4ta2 together classed as a + b; CATH 1a31A3 classed as a + b, 1a31A4, 1a35A4, and 1k4tA4 classed together as a), and the insert domain (SCOP d1k4ta1 classed as a; CATH includes this as part of the catalytic core).

What the Structure Tells Us

Structures associated with human DNA topoisomerase I can be viewed using AstexViewer®, which is linked from the Match Table via the logo on the InterPro page (please note, there is no link directly from this page to the AstexViewer®, therefore you need to go to the link on the InterPro page for P11387). The AstexViewer® displays the PDB structure with the specific CATH or SCOP domain highlighted.

There are structures available for various DNA topoisomerases from several different species in the Protein Data Bank (PDB). A detailed description and visualisation of the structural features of DNA topoisomerases can be found at the PDB ‘Molecule of the Month’. The crystallographic structures of different topoisomerases have provided insight into the different mechanisms of action of these important enzymes.

Next: Table of DNA Topoisomerase Enzymes

Previous: Functions of DNA Topoisomerases