| Human topoisomerase I C-terminal domain fragment containing the active site tyrosine is a molten globule: implication for the formation of competent productive complex. | |
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MedLine Citation:
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PMID: 17434318 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human topoisomerase I (topo I) is an essential cellular enzyme that relaxes DNA supercoiling. The 6.3 kDa C-terminal domain of topo I contains the active site tyrosine (Tyr723) but lacks enzymatic activity by itself. Activity can be fully reconstituted when the C-terminal domain is associated with the 56 kDa core domain. Even though several crystal structures of topo I/DNA complexes are available, crystal structures of the free topo I protein or its individual domain fragments have been difficult to obtain. In this report we analyze the human topo I C-terminal domain structure using a variety of biophysical methods. Our results indicate that this fragment protein (topo6.3) appears to be in a molten globule state. It appears to have a native-like tertiary fold that contains a large population of alpha-helix secondary structure and extensive surface hydrophobic regions. Topo6.3 is known to be readily activated with the association of the topo I core domain, and the molten globule state of topo6.3 is likely to be an energy-favorable conformation for the free topo I C-terminal domain protein. The structural fluctuation and plasticity may represent an efficient mechanism in the topo I functional pathway, where the flexibility aids in the complementary association with the core domain and in the formation of a fully productive topo I complex. |
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Authors:
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Chandanamali Punchihewa; Jixun Dai; Megan Carver; Danzhou Yang |
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Publication Detail:
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Type: Journal Article Date: 2007-03-12 |
Journal Detail:
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Title: Journal of structural biology Volume: 159 ISSN: 1047-8477 ISO Abbreviation: J. Struct. Biol. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-13 Completed Date: 2007-08-30 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 9011206 Medline TA: J Struct Biol Country: United States |
Other Details:
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Languages: eng Pagination: 111-21 Citation Subset: IM |
Affiliation:
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College of Pharmacy, The University of Arizona, 1703 E. Mabel Street, Tucson, AZ 85721, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites DNA Topoisomerases, Type I / chemistry* Humans Hydrophobicity Peptide Fragments / chemistry Pliability Protein Structure, Tertiary Tyrosine* |
| Grant Support | |
ID/Acronym/Agency:
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K01 CA083886-02/CA/NCI NIH HHS; K01 CA083886-03/CA/NCI NIH HHS; K01 CA083886-04/CA/NCI NIH HHS; K01 CA083886-05/CA/NCI NIH HHS; K01 CA083886-06/CA/NCI NIH HHS; S10 RR016659-01/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Peptide Fragments; 55520-40-6/Tyrosine; EC 5.99.1.2/DNA Topoisomerases, Type I |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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