4ENO

Crystal structure of oxidized human nm23-H1

4ENO の概要

• エントリーDOI: 10.2210/pdb4eno/pdb
• 分子名称: Nucleoside diphosphate kinase A, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: ferredoxin-like/alpha, beta proteins, nucleoside diphosphate kinase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34531.38

構造登録者

Kim, M.-S.,Shin, D.-H. (登録日: 2012-04-13, 公開日: 2013-03-27, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)