3UBD

Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101

3UBD の概要

• エントリーDOI: 10.2210/pdb3ubd/pdb
• 分子名称: Ribosomal protein S6 kinase alpha-3, 5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-3-yl 3,4-di-O-acetyl-6-deoxy-alpha-L-mannopyranoside (3 entities in total)
• 機能のキーワード: kinase-inhibitor complex, induced fit, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Nucleus : P18654
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35516.21

構造登録者

Utepbergenov, D.,Derewenda, U.,Derewenda, Z.S. (登録日: 2011-10-24, 公開日: 2012-09-05, 最終更新日: 2023-09-13)

主引用文献

Utepbergenov, D.,Derewenda, U.,Olekhnovich, N.,Szukalska, G.,Banerjee, B.,Hilinski, M.K.,Lannigan, D.A.,Stukenberg, P.T.,Derewenda, Z.S.
Insights into the Inhibition of the p90 Ribosomal S6 Kinase (RSK) by the Flavonol Glycoside SL0101 from the 1.5 A Crystal Structure of the N-Terminal Domain of RSK2 with Bound Inhibitor.
Biochemistry, 51:6499-6510, 2012

PubMed Abstract: The p90 ribosomal S6 family of kinases (RSK) are potential drug targets, due to their involvement in cancer and other pathologies. There are currently only two known selective inhibitors of RSK, but the basis for selectivity is not known. One of these inhibitors is a naturally occurring kaempferol-α-L-diacetylrhamnoside, SL0101. Here, we report the crystal structure of the complex of the N-terminal kinase domain of the RSK2 isoform with SL0101 at 1.5 Å resolution. The refined atomic model reveals unprecedented structural reorganization of the protein moiety, as compared to the nucleotide-bound form. The entire N-lobe, the hinge region, and the αD-helix undergo dramatic conformational changes resulting in a rearrangement of the nucleotide binding site with concomitant formation of a highly hydrophobic pocket spatially suited to accommodate SL0101. These unexpected results will be invaluable in further optimization of the SL0101 scaffold as a promising lead for a novel class of kinase inhibitors.

PubMed: 22846040
DOI: 10.1021/bi300620c

実験手法

X-RAY DIFFRACTION (1.53 Å)