The open state of human topoisomerase I as probed by molecular dynamics simulation
| Autor: | Giovanni Chillemi, Paola Fiorani, Alessandro Desideri, Alessandro Bruselles, Susana Bueno |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Conformational change Protein Conformation Protein domain Type I chemistry DNA topoisomerase article binding site chemical structure computer simulation human protein conformation Binding Sites Computer Simulation DNA Topoisomerases Type I Eukaryotic Humans Molecular dynamics Protein structure Models Structural Biology Genetics Binding site biology Settore BIO/11 Oligonucleotide Molecular Active site Molecular biology Crystallography DNA Topoisomerases Type I biology.protein Eukaryotic DNA supercoil DNA Topoisomerases |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | The open state of human topoisomerase I has been probed by molecular dynamics simulation, starting from the coordinates of the closed structure of the protein complexed with DNA, after elimination of the 22- bp DNA duplex oligonucleotide. A repulsion force between the two lips of the protein has been introduced for a short time to induce destabilization of the local minimum, after which an unperturbed simulation has been carried out for 10 ns. The simulation shows that the protein undergoes a large conformational change due to rearrangements in the orientation of the protein domains, which however move as a coherent unit, fully maintaining their secondary and tertiary structures. Despite movements between the domains as large as 80 - 90 angstrom, the catalytic pentad remains preassembled, the largest deviation of the active site backbone atoms from the starting crystallographic structure being only 1.7 angstrom. Electrostatic calculation of the open protein structure shows that the protein displays a vast positive region with the active site residues located nearly at its center, in a conformation perfectly suited to interact with the negatively charged supercoiled DNA substrate. |
| Databáze: | OpenAIRE |
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