| Structural highlights
Function
[DSP1_ARATH] Possesses phosphotyrosine phosphatase activity in vitro. Hydrolyzes para-nitrophenyl phosphate in vitro (PubMed:21409566, PubMed:18433060). Hydrolyzes O-methylfluorescein phosphate in vitro (PubMed:21409566). Hydrolyzes polyphosphate and ATP in vitro (PubMed:18433060). Dephosphorylates the phosphoinositides PI(3,4,5)P3, PI(3,5)P2, but not PI(3)P, PI(3,4)P2 or PI(4,5)P2 (PubMed:17976645).[1] [2] [3]
Publication Abstract from PubMed
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.
A structural expose of noncanonical molecular reactivity within the protein tyrosine phosphatase WPD loop.,Wang H, Perera L, Jork N, Zong G, Riley AM, Potter BVL, Jessen HJ, Shears SB Nat Commun. 2022 Apr 25;13(1):2231. doi: 10.1038/s41467-022-29673-y. PMID:35468885[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Roma-Mateo C, Rios P, Tabernero L, Attwood TK, Pulido R. A novel phosphatase family, structurally related to dual-specificity phosphatases, that displays unique amino acid sequence and substrate specificity. J Mol Biol. 2007 Dec 7;374(4):899-909. doi: 10.1016/j.jmb.2007.10.008. Epub 2007 , Oct 11. PMID:17976645 doi:http://dx.doi.org/10.1016/j.jmb.2007.10.008
- ↑ Aceti DJ, Bitto E, Yakunin AF, Proudfoot M, Bingman CA, Frederick RO, Sreenath HK, Vojtik FC, Wrobel RL, Fox BG, Markley JL, Phillips GN Jr. Structural and functional characterization of a novel phosphatase from the Arabidopsis thaliana gene locus At1g05000. Proteins. 2008 Oct;73(1):241-53. PMID:18433060 doi:10.1002/prot.22041
- ↑ Roma-Mateo C, Sacristan-Reviriego A, Beresford NJ, Caparros-Martin JA, Culianez-Macia FA, Martin H, Molina M, Tabernero L, Pulido R. Phylogenetic and genetic linkage between novel atypical dual-specificity phosphatases from non-metazoan organisms. Mol Genet Genomics. 2011 Apr;285(4):341-54. doi: 10.1007/s00438-011-0611-6. Epub , 2011 Mar 16. PMID:21409566 doi:http://dx.doi.org/10.1007/s00438-011-0611-6
- ↑ Wang H, Perera L, Jork N, Zong G, Riley AM, Potter BVL, Jessen HJ, Shears SB. A structural expose of noncanonical molecular reactivity within the protein tyrosine phosphatase WPD loop. Nat Commun. 2022 Apr 25;13(1):2231. doi: 10.1038/s41467-022-29673-y. PMID:35468885 doi:http://dx.doi.org/10.1038/s41467-022-29673-y
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