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- Publisher Website: 10.1016/j.abb.2011.10.008
- Scopus: eid_2-s2.0-81755174145
- PMID: 22033340
- WOS: WOS:000297716700004
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Article: Inhibition of human DNA topoisomerase IB by a Cyclometalated Gold III compound: Analysis on the different steps of the enzyme catalytic cycle
Title | Inhibition of human DNA topoisomerase IB by a Cyclometalated Gold III compound: Analysis on the different steps of the enzyme catalytic cycle |
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Authors | |
Keywords | Anticancer drug Camptothecin Cyclometalated gold(III) compound Human DNA topoisomerase IB Inhibition |
Issue Date | 2011 |
Publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/yabbi |
Citation | Archives Of Biochemistry And Biophysics, 2011, v. 516 n. 2, p. 108-112 How to Cite? |
Abstract | A gold(III) compound [Au(CNC)(IMe)]CF 3SO 3 (Gold III) has been reported to have anticancer properties as it is able to reduce topoisomerase IB activity in vitro and suppress tumor growth in nude mice model. Here we have investigated the mechanism of inhibition of human topoisomerase IB activity by this compound, analyzing the various steps of the catalytic cycle. DNA supercoiled relaxation and the cleavage reaction are inhibited, but Gold III does not perturb the religation reaction, in contrast to what has been observed for camptothecin. Pre-incubation of enzyme with the inhibitor before adding DNA substrate increases the inhibitory effect. In addition, when Gold III is preincubated with the enzyme it prevents the stabilization of the cleavable complex by camptothecin. The analysis of the DNA-topoisomerase binding reaction indicates that the compound acts as a topoisomerase I inhibitor by preventing the enzyme-DNA interaction. |
Persistent Identifier | http://hdl.handle.net/10722/168590 |
ISSN | 2021 Impact Factor: 4.114 2020 SCImago Journal Rankings: 1.097 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Castelli, S | en_US |
dc.contributor.author | Vassallo, O | en_US |
dc.contributor.author | Katkar, P | en_US |
dc.contributor.author | Che, CM | en_US |
dc.contributor.author | Sun, RWY | en_US |
dc.contributor.author | Desideri, A | en_US |
dc.date.accessioned | 2012-10-08T03:21:14Z | - |
dc.date.available | 2012-10-08T03:21:14Z | - |
dc.date.issued | 2011 | en_US |
dc.identifier.citation | Archives Of Biochemistry And Biophysics, 2011, v. 516 n. 2, p. 108-112 | en_US |
dc.identifier.issn | 0003-9861 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/168590 | - |
dc.description.abstract | A gold(III) compound [Au(CNC)(IMe)]CF 3SO 3 (Gold III) has been reported to have anticancer properties as it is able to reduce topoisomerase IB activity in vitro and suppress tumor growth in nude mice model. Here we have investigated the mechanism of inhibition of human topoisomerase IB activity by this compound, analyzing the various steps of the catalytic cycle. DNA supercoiled relaxation and the cleavage reaction are inhibited, but Gold III does not perturb the religation reaction, in contrast to what has been observed for camptothecin. Pre-incubation of enzyme with the inhibitor before adding DNA substrate increases the inhibitory effect. In addition, when Gold III is preincubated with the enzyme it prevents the stabilization of the cleavable complex by camptothecin. The analysis of the DNA-topoisomerase binding reaction indicates that the compound acts as a topoisomerase I inhibitor by preventing the enzyme-DNA interaction. | en_US |
dc.language | eng | en_US |
dc.publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/yabbi | en_US |
dc.relation.ispartof | Archives of Biochemistry and Biophysics | en_US |
dc.subject | Anticancer drug | - |
dc.subject | Camptothecin | - |
dc.subject | Cyclometalated gold(III) compound | - |
dc.subject | Human DNA topoisomerase IB | - |
dc.subject | Inhibition | - |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Antineoplastic Agents - Chemistry - Pharmacology | en_US |
dc.subject.mesh | Catalysis | en_US |
dc.subject.mesh | Dna - Metabolism | en_US |
dc.subject.mesh | Dna Topoisomerases, Type I - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Electrophoretic Mobility Shift Assay | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Kinetics | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Organogold Compounds - Chemistry - Pharmacology | en_US |
dc.subject.mesh | Recombinant Proteins - Antagonists & Inhibitors - Metabolism | en_US |
dc.subject.mesh | Substrate Specificity | en_US |
dc.subject.mesh | Topoisomerase I Inhibitors - Chemistry - Pharmacology | en_US |
dc.title | Inhibition of human DNA topoisomerase IB by a Cyclometalated Gold III compound: Analysis on the different steps of the enzyme catalytic cycle | en_US |
dc.type | Article | en_US |
dc.identifier.email | Che, CM:cmche@hku.hk | en_US |
dc.identifier.email | Sun, RWY:rwysun@hku.hk | en_US |
dc.identifier.authority | Che, CM=rp00670 | en_US |
dc.identifier.authority | Sun, RWY=rp00781 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1016/j.abb.2011.10.008 | en_US |
dc.identifier.pmid | 22033340 | - |
dc.identifier.scopus | eid_2-s2.0-81755174145 | en_US |
dc.identifier.hkuros | 205051 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-81755174145&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 516 | en_US |
dc.identifier.issue | 2 | en_US |
dc.identifier.spage | 108 | en_US |
dc.identifier.epage | 112 | en_US |
dc.identifier.isi | WOS:000297716700004 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Castelli, S=35270975600 | en_US |
dc.identifier.scopusauthorid | Vassallo, O=18435432000 | en_US |
dc.identifier.scopusauthorid | Katkar, P=54585391500 | en_US |
dc.identifier.scopusauthorid | Che, CM=7102442791 | en_US |
dc.identifier.scopusauthorid | Sun, RWY=26325835800 | en_US |
dc.identifier.scopusauthorid | Desideri, A=35430278400 | en_US |
dc.identifier.citeulike | 9933134 | - |
dc.identifier.issnl | 0003-9861 | - |