7MOD

Crystal Structure of Arabidopsis thaliana Plant and Fungi Atypical Dual Specificity Phosphatase 1(AtPFA-DSP1 ) Cys150Ser in Complex with Phosphate in Conformation A (Pi(A))

7MOD の概要

• エントリーDOI: 10.2210/pdb7mod/pdb
• 分子名称: Tyrosine-protein phosphatase DSP1, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: inositol, inositol pyrophosphate, transferase, hydrolase, cell-signaling, phosphatase, substrate recognition, reaction mechanism, intermediate, phosphate, metaphosphate, molecular dynamic simulation, self-activation, catalytic water
• 由来する生物種: Arabidopsis thaliana (Mouse-ear cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39475.48

構造登録者

Wang, H.,Shears, S.B. (登録日: 2021-05-01, 公開日: 2022-03-02, 最終更新日: 2023-10-18)

主引用文献

Wang, H.,Perera, L.,Jork, N.,Zong, G.,Riley, A.M.,Potter, B.V.L.,Jessen, H.J.,Shears, S.B.
A structural expose of noncanonical molecular reactivity within the protein tyrosine phosphatase WPD loop.
Nat Commun, 13:2231-2231, 2022

PubMed Abstract: Structural snapshots of protein/ligand complexes are a prerequisite for gaining atomic level insight into enzymatic reaction mechanisms. An important group of enzymes has been deprived of this analytical privilege: members of the protein tyrosine phosphatase (PTP) superfamily with catalytic WPD-loops lacking the indispensable general-acid/base within a tryptophan-proline-aspartate/glutamate context. Here, we provide the ligand/enzyme crystal complexes for one such PTP outlier: Arabidopsis thaliana Plant and Fungi Atypical Dual Specificity Phosphatase 1 (AtPFA-DSP1), herein unveiled as a regioselective and efficient phosphatase towards inositol pyrophosphate (PP-InsP) signaling molecules. Although the WPD loop is missing its canonical tripeptide motif, this structural element contributes to catalysis by assisting PP-InsP delivery into the catalytic pocket, for a choreographed exchange with phosphate reaction product. Subsequently, an intramolecular proton donation by PP-InsP substrate is posited to substitute functionally for the absent aspartate/glutamate general-acid. Overall, we expand mechanistic insight into adaptability of the conserved PTP structural elements.

PubMed: 35468885
DOI: 10.1038/s41467-022-29673-y

実験手法

X-RAY DIFFRACTION (1.65 Å)