6OID

Redox Regulation of FN3K from Arabidopsis thaliana

6OID の概要

• エントリーDOI: 10.2210/pdb6oid/pdb
• 分子名称: Protein-ribulosamine 3-kinase, chloroplastic, ADENOSINE-5'-DIPHOSPHATE, SULFATE ION, ... (7 entities in total)
• 機能のキーワード: kinase, fructosamine-3-kinase, small molecule kinase, protein repair, phosphotransferase, deglycation, plant protein, transferase
• 由来する生物種: Arabidopsis thaliana (Mouse-ear cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73670.59

構造登録者

Wood, Z.A.,Kadirvelraj, R.,Shrestha, S. (登録日: 2019-04-09, 公開日: 2020-05-20, 最終更新日: 2024-10-30)

主引用文献

Shrestha, S.,Katiyar, S.,Sanz-Rodriguez, C.E.,Kemppinen, N.R.,Kim, H.W.,Kadirvelraj, R.,Panagos, C.,Keyhaninejad, N.,Colonna, M.,Chopra, P.,Byrne, D.P.,Boons, G.J.,van der Knaap, E.,Eyers, P.A.,Edison, A.S.,Wood, Z.A.,Kannan, N.
A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily.
Sci.Signal., 13:-, 2020

PubMed Abstract: Aberrant regulation of metabolic kinases by altered redox homeostasis substantially contributes to aging and various diseases, such as diabetes. We found that the catalytic activity of a conserved family of fructosamine-3-kinases (FN3Ks), which are evolutionarily related to eukaryotic protein kinases, is regulated by redox-sensitive cysteine residues in the kinase domain. The crystal structure of the FN3K homolog from revealed that it forms an unexpected strand-exchange dimer in which the ATP-binding P-loop and adjoining β strands are swapped between two chains in the dimer. This dimeric configuration is characterized by strained interchain disulfide bonds that stabilize the P-loop in an extended conformation. Mutational analysis and solution studies confirmed that the strained disulfides function as redox "switches" to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, was also redox sensitive, whereas ancestral bacterial FN3K homologs, which lack a P-loop Cys, were not. Furthermore, CRISPR-mediated knockout of FN3K in human liver cancer cells altered the abundance of redox metabolites, including an increase in glutathione. We propose that redox regulation evolved in FN3K homologs in response to changing cellular redox conditions. Our findings provide insights into the origin and evolution of redox regulation in the protein kinase superfamily and may open new avenues for targeting human FN3K in diabetic complications.

PubMed: 32636308
DOI: 10.1126/scisignal.aax6313

実験手法

X-RAY DIFFRACTION (2.365 Å)