7MOH

Crystal Structure of Arabidopsis thaliana Plant and Fungi Atypical Dual Specificity Phosphatase 1(AtPFA-DSP1 ) Cys150Ser in complex with 5-diphosphoinositol 1,3,4,6-tetrakisphosphate (5PP-InsP4) and phosphate in conformation B (Pi(B))

Summary for 7MOH

• Entry DOI: 10.2210/pdb7moh/pdb
• Descriptor: Tyrosine-protein phosphatase DSP1, (1r,2R,3S,4r,5R,6S)-4-hydroxy-2,3,5,6-tetrakis(phosphonooxy)cyclohexyl trihydrogen diphosphate, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: inositol, inositol pyrophosphate, transferase, hydrolase, cell-signaling, phosphatase, substrate recognition, reaction mechanism, intermediate, phosphate, metaphosphate, molecular dynamic simulation, self-activation, catalytic water
• Biological source: Arabidopsis thaliana (Mouse-ear cress)
• Total number of polymer chains: 2
• Total formula weight: 40700.58

Authors

Wang, H.,Shears, S.B. (deposition date: 2021-05-01, release date: 2022-03-02, Last modification date: 2024-05-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)