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Structure of Nm23-H1 under oxidative conditions

Title
Structure of Nm23-H1 under oxidative conditions
Authors
Kim M.-S.Jeong J.Shin D.-H.Lee K.-J.
Ewha Authors
이공주신동해
SCOPUS Author ID
이공주scopus; 신동해scopus
Issue Date
2013
Journal Title
Acta Crystallographica Section D: Biological Crystallography
ISSN
0907-4449JCR Link
Citation
vol. 69, no. 4, pp. 669 - 680
Indexed
SCOPUS WOS scopus
Abstract
Nm23-H1/NDPK-A, a tumour metastasis suppressor, is a multifunctional housekeeping enzyme with nucleoside diphosphate kinase activity. Hexameric Nm23-H1 is required for suppression of tumour metastasis and it is dissociated into dimers under oxidative conditions. Here, the crystal structure of oxidized Nm23-H1 is presented. It reveals the formation of an intramolecular disulfide bond between Cys4 and Cys145 that triggers a large conformational change that destabilizes the hexameric state. The dependence of the dissociation dynamics on the H2O2 concentration was determined using hydrogen/deuterium-exchange experiments. The quaternary conformational change provides a suitable environment for the oxidation of Cys109 to sulfonic acid, as demonstrated by peptide sequencing using nanoUPLC-ESI-q-TOF tandem MS. From these and other data, it is proposed that the molecular and cellular functions of Nm23-H1 are regulated by a series of oxidative modifications coupled to its oligomeric states and that the modified cysteines are resolvable by NADPH-dependent reduction systems. These findings broaden the understanding of the complicated enzyme-regulatory mechanisms that operate under oxidative conditions. © 2013 International Union of Crystallography Printed in Singapore - all rights reserved.
DOI
10.1107/S0907444913001194
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약학대학 > 약학과 > Journal papers
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