2WO6

Human Dual-Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A in complex with a consensus substrate peptide

2WO6 の概要

• エントリーDOI: 10.2210/pdb2wo6/pdb
• 関連するPDBエントリー: 2VX3
• 分子名称: DUAL SPECIFICITY TYROSINE-PHOSPHORYLATION- REGULATED KINASE 1A, ARTIFICIAL CONSENSUS SEQUENCE, N-(5-{[(2S)-4-amino-2-(3-chlorophenyl)butanoyl]amino}-1H-indazol-3-yl)benzamide, ... (5 entities in total)
• 機能のキーワード: transferase-peptide complex, transferase peptide complex, serine/threonine-protein atp-binding, phosphoprotein, nucleotide-binding, dyrk1, dyrk1a, kinase, nucleus, transferase, tyrosine-protein kinase, transferase/peptide
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus speckle: Q13627
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 90820.57

構造登録者

Roos, A.K.,Soundararajan, M.,Elkins, J.M.,Fedorov, O.,Eswaran, J.,Phillips, C.,Pike, A.C.W.,Ugochukwu, E.,Muniz, J.R.C.,Burgess-Brown, N.,von Delft, F.,Arrowsmith, C.H.,Wikstrom, M.,Edwards, A.,Bountra, C.,Knapp, S. (登録日: 2009-07-22, 公開日: 2009-08-18, 最終更新日: 2024-11-20)

主引用文献

Soundararajan, M.,Roos, A.K.,Savitsky, P.,Filippakopoulos, P.,Kettenbach, A.N.,Olsen, J.V.,Gerber, S.A.,Eswaran, J.,Knapp, S.,Elkins, J.M.
Structures of Down Syndrome Kinases, Dyrks, Reveal Mechanisms of Kinase Activation and Substrate Recognition.
Structure, 21:986-, 2013

PubMed Abstract: Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinases (DYRKs) play key roles in brain development, regulation of splicing, and apoptosis, and are potential drug targets for neurodegenerative diseases and cancer. We present crystal structures of one representative member of each DYRK subfamily: DYRK1A with an ATP-mimetic inhibitor and consensus peptide, and DYRK2 including NAPA and DH (DYRK homology) box regions. The current activation model suggests that DYRKs are Ser/Thr kinases that only autophosphorylate the second tyrosine of the activation loop YxY motif during protein translation. The structures explain the roles of this tyrosine and of the DH box in DYRK activation and provide a structural model for DYRK substrate recognition. Phosphorylation of a library of naturally occurring peptides identified substrate motifs that lack proline in the P+1 position, suggesting that DYRK1A is not a strictly proline-directed kinase. Our data also show that DYRK1A wild-type and Y321F mutant retain tyrosine autophosphorylation activity.

PubMed: 23665168
DOI: 10.1016/J.STR.2013.03.012

実験手法

X-RAY DIFFRACTION (2.5 Å)