Structure of Nm23-H1 under oxidative conditions

Mi Sun Kim, Jaeho Jeong, Jihye Jeong, Dong Hae Shin, Kong Joo Lee

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish
Pages (from-to)669-680
Number of pages12
JournalActa Crystallographica Section D: Biological Crystallography
Issue number4
StatePublished - Apr 2013


Dive into the research topics of 'Structure of Nm23-H1 under oxidative conditions'. Together they form a unique fingerprint.

Cite this