User:Isabelle Kressy/Sandbox 1
From Proteopedia
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== Evolutionarily Related Proteins == | == Evolutionarily Related Proteins == | ||
- | <Structure load='4Z2D' size='350' frame='true' align='left' caption='Gyrase DNA cleavage complex with Quinolone' /> | + | <Structure load='4Z2D' size='350' frame='true' align='left' caption='Gyrase DNA cleavage complex with Quinolone'/> |
+ | Topo IV works closely with gyrase, another type II topoisomerase, to uncoil DNA and ensure that replication can take place. Its main function is to relax positive supercoils and catalyze the formation of negative supercoils. Unlike topo IV, gyrase cannot unknot and decatenate DNA. Structurally, these two topoisomerases are very similar. One study found that the E. coli CTD of the ParC subunit is a degenerate form of the CTD in gyrase and that it is positioned differently for substrate specificity. | ||
== Available Structures == | == Available Structures == |
Revision as of 03:26, 3 May 2022
Contents |
Quinolone(Clinafloxacin)-DNA cleavage complex of type IV topoisomerase from S. pneumoniae
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Topoisomerase IV in S. pneumoniae is a paralogue of type II topoisomerase. This structure is a complex of topoisomerase, DNA, and Quinolone, a drug that targets type II topoisomerases in Gram-negative and Gram-positive bacteria [1]. Topoisomerase IV consists of two subunits that function to regulate supercoiling and disentangle DNA.
Function
The main function of topoisomerase IV is to regulate the level of DNA supercoiling within the cell so that replication, transcription, and repair can take place [2].
In general, type II topoisomerases undergo a strand-passage mechanism to remove supercoiling and disentangle chromosomes. These enzymes cleave both strands of DNA and then pass a second duplex through the break using ATP. The cleaved strands are ligated together again and the two products are released from the enzyme [3].
Structural Description
The active site is a tetramer made up of and subunits. The ParC subunit contains an N-terminal DNA breakage-reunion domain, which is linked to C-terminal β-pinwheel domains. This favors the passage of DNA and DNA unlinking from the complex. In contrast, the N-terminal of the ParE subunits forms the ATPase domain. Topoisomerase IV forms a complex with gyrase and works in tandem to remove DNA supercoiling and disentangle chromosomes.
Structure Insights
Evolutionarily Related Proteins
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Topo IV works closely with gyrase, another type II topoisomerase, to uncoil DNA and ensure that replication can take place. Its main function is to relax positive supercoils and catalyze the formation of negative supercoils. Unlike topo IV, gyrase cannot unknot and decatenate DNA. Structurally, these two topoisomerases are very similar. One study found that the E. coli CTD of the ParC subunit is a degenerate form of the CTD in gyrase and that it is positioned differently for substrate specificity.
Available Structures
</StructureSection>
References
- ↑ Laponogov I, Pan XS, Veselkov DA, Cirz RT, Wagman A, Moser HE, Fisher LM, Sanderson MR. Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones. Open Biol. 2016 Sep;6(9). pii: rsob.160157. doi: 10.1098/rsob.160157. PMID:27655731 doi:http://dx.doi.org/10.1098/rsob.160157
- ↑ Laponogov I, Pan XS, Veselkov DA, Cirz RT, Wagman A, Moser HE, Fisher LM, Sanderson MR. Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones. Open Biol. 2016 Sep;6(9). pii: rsob.160157. doi: 10.1098/rsob.160157. PMID:27655731 doi:http://dx.doi.org/10.1098/rsob.160157
- ↑ Laponogov I, Veselkov DA, Crevel IM, Pan XS, Fisher LM, Sanderson MR. Structure of an 'open' clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport. Nucleic Acids Res. 2013 Aug 21. PMID:23965305 doi:10.1093/nar/gkt749