dc.contributor.author | D'Annessa, I | |
dc.contributor.author | Coletta, A | |
dc.contributor.author | Sutthibutpong, T | |
dc.contributor.author | Mitchell, J | |
dc.contributor.author | Chillemi, G | |
dc.contributor.author | Harris, S | |
dc.contributor.author | Desideri, A | |
dc.date.accessioned | 2018-06-13T10:07:14Z | |
dc.date.issued | 2014-08-18 | |
dc.identifier | http://nar.oxfordjournals.org/content/42/14/9304 | |
dc.identifier.citation | NUCLEIC ACIDS RESEARCH, 2014, 42 (14), pp. 9304 - 9312 | |
dc.identifier.issn | 0305-1048 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1852 | |
dc.description.abstract | Human topoisomerase 1B has been simulated covalently bound to a negatively supercoiled DNA minicircle, and its behavior compared to the enzyme bound to a simple linear DNA duplex. The presence of the more realistic supercoiled substrate facilitates the formation of larger number of protein-DNA interactions when compared to a simple linear duplex fragment. The number of protein-DNA hydrogen bonds doubles in proximity to the active site, affecting all of the residues in the catalytic pentad. The clamp over the DNA, characterized by the salt bridge between Lys369 and Glu497, undergoes reduced fluctuations when bound to the supercoiled minicircle. The linker domain of the enzyme, which is implicated in the controlled relaxation of superhelical stress, also displays an increased number of contacts with the minicircle compared to linear DNA. Finally, the more complex topology of the supercoiled DNA minicircle gives rise to a secondary DNA binding site involving four residues located on subdomain III. The simulation trajectories reveal significant changes in the interactions between the enzyme and the DNA for the more complex DNA topology, which are consistent with the experimental observation that the protein has a preference for binding to supercoiled DNA. | |
dc.format.extent | 9304 - 9312 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Oxford University Press (OUP) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | MOLECULAR-DYNAMICS SIMULATIONS CAMPTOTHECIN RESISTANCE VACCINIA TOPOISOMERASE PREFERENTIAL BINDING CRYSTAL-STRUCTURES LINKER DOMAIN MECHANISM IB EFFICIENT COVALENT | |
dc.title | Simulations of DNA topoisomerase 1B bound to supercoiled DNA reveal changes in the flexibility pattern of the enzyme and a secondary protein–DNA binding site | |
dc.type | Journal Article | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2014 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | NUCLEIC ACIDS RESEARCH | |
pubs.issue | 14 | |
pubs.notes | ISI Document Delivery No.: AQ9ZH Times Cited: 0 Cited Reference Count: 42 D'Annessa, Ilda Coletta, Andrea Sutthibutpong, Thana Mitchell, Jonathan Chillemi, Giovanni Harris, Sarah Desideri, Alessandro Associazione Italiana Ricerca Cancro (AIRC) [10121, BB/I019472/1] Associazione Italiana Ricerca Cancro (AIRC) with the Grant No. 10121 to AD. Funding for open access charge: Associazione Italiana Ricerca Cancro (AIRC) with the Grant No. 10121 to AD and the Grant No. BB/I019472/1 to SH. 0 OXFORD UNIV PRESS OXFORD NUCLEIC ACIDS RES | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Molecular & Population Genetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Molecular & Population Genetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics | |
pubs.volume | 42 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular & Population Genetics | |
dc.contributor.icrauthor | Mitchell, Jonathan | |