1GKX

Branched-chain alpha-ketoacid dehydrogenase kinase (BCK)

1GKX の概要

• エントリーDOI: 10.2210/pdb1gkx/pdb
• 関連するPDBエントリー: 1GJV
• 分子名称: [3-METHYL-2-OXOBUTANOATE DEHYDROGENASE [LIPOAMIDE]] KINASE, CHLORIDE ION (3 entities in total)
• 機能のキーワード: transferase, mitochondrial protein kinase, potassium
• 由来する生物種: RATTUS NORVEGICUS (RAT)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44403.39

構造登録者

Machius, M.,Chuang, J.L.,Wynn, R.M.,Tomchick, D.R.,Chuang, D.T. (登録日: 2001-08-21, 公開日: 2001-10-11, 最終更新日: 2024-05-01)

主引用文献

Machius, M.,Chuang, J.L.,Wynn, R.M.,Tomchick, D.R.,Chuang, D.T.
Structure of Rat Bckd Kinase: Nucleotide-Induced Domain Communication in a Mitochondrial Protein Kinase.
Proc.Natl.Acad.Sci.USA, 98:11218-, 2001

PubMed Abstract: Mitochondrial protein kinases (mPKs) are molecular switches that down-regulate the oxidation of branched-chain alpha-ketoacids and pyruvate. Elevated levels of these metabolites are implicated in disease states such as insulin-resistant Type II diabetes, branched-chain ketoaciduria, and primary lactic acidosis. We report a three-dimensional structure of a member of the mPK family, rat branched-chain alpha-ketoacid dehydrogenase kinase (BCK). BCK features a characteristic nucleotide-binding domain and a four-helix bundle domain. These two domains are reminiscent of modules found in protein histidine kinases (PHKs), which are involved in two-component signal transduction systems. Unlike PHKs, BCK dimerizes through direct interaction of two opposing nucleotide-binding domains. Nucleotide binding to BCK is uniquely mediated by both potassium and magnesium. Binding of ATP induces disorder-order transitions in a loop region at the nucleotide-binding site. These structural changes lead to the formation of a quadruple aromatic stack in the interface between the nucleotide-binding domain and the four-helix bundle domain, where they induce a movement of the top portion of two helices. Phosphotransfer induces further ordering of the loop region, effectively trapping the reaction product ADP, which explains product inhibition in mPKs. The BCK structure is a prototype for all mPKs and will provide a framework for structure-assisted inhibitor design for this family of kinases.

PubMed: 11562470
DOI: 10.1073/PNAS.201220098

実験手法

X-RAY DIFFRACTION (2.3 Å)