4JDK

Crystal structure of Serine/threonine-protein kinase PAK 4 F461V mutant in complex with Paktide S peptide substrate

4JDK の概要

• エントリーDOI: 10.2210/pdb4jdk/pdb
• 関連するPDBエントリー: 4FIJ 4JDH 4JDI 4JDJ
• 分子名称: Serine/threonine-protein kinase PAK 4, Paktide S (3 entities in total)
• 機能のキーワード: transferase-peptide complex, transferase/peptide, serine/threonine-protein kinase pak4, atp binding, phosphorylation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: O96013
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40238.32

構造登録者

Ha, B.H.,Boggon, T.J. (登録日: 2013-02-25, 公開日: 2014-01-29, 最終更新日: 2023-09-20)

主引用文献

Chen, C.,Ha, B.H.,Thevenin, A.F.,Lou, H.J.,Zhang, R.,Yip, K.Y.,Peterson, J.R.,Gerstein, M.,Kim, P.M.,Filippakopoulos, P.,Knapp, S.,Boggon, T.J.,Turk, B.E.
Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.
Mol.Cell, 53:140-147, 2014

PubMed Abstract: Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue located in the kinase activation segment, which we term the "DFG+1" residue, acts as a major determinant for serine-threonine phosphorylation site specificity. Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4. Kinetic analysis of peptide substrate phosphorylation and crystal structures of PAK4-peptide complexes suggested that phosphoacceptor residue preference is not mediated by stronger binding of the favored substrate. Rather, favored kinase-phosphoacceptor combinations likely promote a conformation optimal for catalysis. Understanding the rules governing kinase phosphoacceptor preference allows kinases to be classified as serine or threonine specific based on their sequence.

PubMed: 24374310
DOI: 10.1016/j.molcel.2013.11.013

実験手法

X-RAY DIFFRACTION (2.4 Å)