4ENO

Crystal structure of oxidized human nm23-H1

Summary for 4ENO

• Entry DOI: 10.2210/pdb4eno/pdb
• Descriptor: Nucleoside diphosphate kinase A, PHOSPHATE ION (3 entities in total)
• Functional Keywords: ferredoxin-like/alpha, beta proteins, nucleoside diphosphate kinase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 34531.38

Authors

Kim, M.-S.,Shin, D.-H. (deposition date: 2012-04-13, release date: 2013-03-27, Last modification date: 2024-10-16)

Primary citation

Kim, M.S.,Jeong, J.,Jeong, J.,Shin, D.H.,Lee, K.J.
Structure of Nm23-H1 under oxidative conditions.
Acta Crystallogr.,Sect.D, 69:669-680, 2013

PubMed 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.

PubMed: 23519676
DOI: 10.1107/S0907444913001194

Experimental method

X-RAY DIFFRACTION (2.8 Å)