Acta Crystallographica Section D

Biological Crystallography

Volume 69, Part 4 (April 2013)


research papers



Acta Cryst. (2013). D69, 669-680    [ doi:10.1107/S0907444913001194 ]

Structure of Nm23-H1 under oxidative conditions

M.-S. Kim, J. Jeong, J. Jeong, D.-H. Shin and K.-J. Lee

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.

PDB reference: 4eno

Keywords: oxidative modification; disulfides; sulfonic acid; conformational change; hydrogen/deuterium exchange; mass spectrometry.


pdfdisplay filedownload file

Portable Document Format (PDF) file
[ doi:10.1107/S0907444913001194/mn5019sup1.pdf ]
Supplementary material


Notes:

To open or display or play some files, you may need to set your browser up to use the appropriate software. See the full list of file types for an explanation of the different file types and their related mime types and, where available links to sites from where the appropriate software may be obtained.

The download button will force most browsers to prompt for a file name to store the data on your hard disk.

Where possible, images are represented by thumbnails.

 bibliographic record in  format

  Find reference:   Volume   Page   
  Search:     From   to      Advanced search

Copyright © International Union of Crystallography
IUCr Webmaster