5ZN5

X-ray structure of protein kinase ck2 alpha subunit H148A mutant

5ZN5 の概要

• エントリーDOI: 10.2210/pdb5zn5/pdb
• 分子名称: Casein kinase II subunit alpha, SULFATE ION (3 entities in total)
• 機能のキーワード: kinase, ck2, human, casein, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39599.13

構造登録者

Shibazaki, C.,Arai, S.,Shimizu, R.,Kinoshita, T.,Kuroki, R.,Adachi, M. (登録日: 2018-04-07, 公開日: 2018-11-21, 最終更新日: 2024-03-27)

主引用文献

Shibazaki, C.,Arai, S.,Shimizu, R.,Saeki, M.,Kinoshita, T.,Ostermann, A.,Schrader, T.E.,Kurosaki, Y.,Sunami, T.,Kuroki, R.,Adachi, M.
Hydration Structures of the Human Protein Kinase CK2 alpha Clarified by Joint Neutron and X-ray Crystallography.
J. Mol. Biol., 430:5094-5104, 2018

PubMed Abstract: Casein kinase 2 (CK2) has broad phosphorylation activity against various regulatory proteins, which are important survival factors in eukaryotic cells. To clarify the hydration structure and catalytic mechanism of CK2, we determined the crystal structure of the alpha subunit of human CK2 containing hydrogen and deuterium atoms using joint neutron (1.9 Å resolution) and X-ray (1.1 Å resolution) crystallography. The analysis revealed the structure of conserved water molecules at the active site and a long potential hydrogen bonding network originating from the catalytic Asp156 that is well known to enhance the nucleophilicity of the substrate OH group to the γ-phospho group of ATP by proton elimination. His148 and Asp214 conserved in the protein kinase family are located in the middle of the network. The water molecule forming a hydrogen bond with Asp214 appears to be deformed. In addition, mutational analysis of His148 in CK2 showed significant reductions by 40%-75% in the catalytic efficiency with similar affinity for ATP. Likewise, remarkable reductions to less than 5% were shown by corresponding mutations on His131 in death-associated protein kinase 1, which belongs to a group different from that of CK2. These findings shed new light on the catalytic mechanism of protein kinases in which the hydrogen bond network through the C-terminal domain may assist the general base catalyst to extract a proton with a link to the bulk solvent via intermediates of a pair of residues.

PubMed: 30359582
DOI: 10.1016/j.jmb.2018.09.018

実験手法

X-RAY DIFFRACTION (1.7 Å)