Abstract:
: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 A, the catalytic pentad remains preassembled, the largest deviation of the active site backbone atoms from the starting crystallographic structure being only 1.7 A. 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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Chillemi G,Bruselles A,Fiorani P,Bueno S,Desideri Adoi
10.1093/nar/gkm199subject
Has Abstractpub_date
2007-01-01 00:00:00pages
3032-8issue
9eissn
0305-1048issn
1362-4962pii
gkm199journal_volume
35pub_type
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