A structural exposé of noncanonical molecular reactivity within the protein tyrosine phosphatase WPD loop
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
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Anmerkungen
-
Nature communications. - 13 (2022) , 2231, ISSN: 2041-1723
- Ereignis
-
Veröffentlichung
- (wo)
-
Freiburg
- (wer)
-
Universität
- (wann)
-
2024
- Urheber
-
Wang, Huanchen
Perera, Lalith
Jork, Nikolaus
Zong, Guangning
Riley, Andrew M.
Potter, Barry V. L.
Jessen, Henning Jacob
Shears, Stephen B.
- DOI
-
10.1038/s41467-022-29673-y
- URN
-
urn:nbn:de:bsz:25-freidok-2448561
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
25.03.2025, 13:41 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Wang, Huanchen
- Perera, Lalith
- Jork, Nikolaus
- Zong, Guangning
- Riley, Andrew M.
- Potter, Barry V. L.
- Jessen, Henning Jacob
- Shears, Stephen B.
- Universität
Entstanden
- 2024
Ähnliche Objekte (12)
Untersuchungen zur intrazellulären Freisetzung von Nucleosidphosphaten
Structural and biochemical characterization of Siw14 : : a protein-tyrosine phosphatase fold that metabolizes inositol pyrophosphates
Activities, substrate specificity, and genetic interactions of fission yeast Siw14, a cysteinyl-phosphatase-type inositol pyrophosphatase
Synthesis of novel photocaged thiamine triphosphate prometabolites and investigations towards an efficient bidirectional synthesis of asymmetric dinucleoside polyphosphates
The 8th young faculty meeting – an active crowd attuned to modern challenges
Rapid synthesis of nucleoside triphosphates and analogues
Design of sensors for highly phosphorylated natural compounds
Novel shades of inositol pyrophosphates – in vitro and in cellulo evaluation of inositol pyrophosphate probes
Synthesis of bisdiphosphoinositol polyphosphate prometabolites
Investigations on the synthesis and degradation of polyphosphate in vitro and its correlation to magic spot nucleotides
Development of novel p-amidites and their application in the synthesis of the most densely phosphorylated compounds
Characterisation of family 2 polyphosphate kinases
Untersuchungen zur intrazellulären Freisetzung von Nucleosidphosphaten
Structural and biochemical characterization of Siw14 : : a protein-tyrosine phosphatase fold that metabolizes inositol pyrophosphates
Activities, substrate specificity, and genetic interactions of fission yeast Siw14, a cysteinyl-phosphatase-type inositol pyrophosphatase
Synthesis of novel photocaged thiamine triphosphate prometabolites and investigations towards an efficient bidirectional synthesis of asymmetric dinucleoside polyphosphates
The 8th young faculty meeting – an active crowd attuned to modern challenges
Rapid synthesis of nucleoside triphosphates and analogues
Design of sensors for highly phosphorylated natural compounds
Novel shades of inositol pyrophosphates – in vitro and in cellulo evaluation of inositol pyrophosphate probes
Synthesis of bisdiphosphoinositol polyphosphate prometabolites
Investigations on the synthesis and degradation of polyphosphate in vitro and its correlation to magic spot nucleotides
Development of novel p-amidites and their application in the synthesis of the most densely phosphorylated compounds
Characterisation of family 2 polyphosphate kinases
Untersuchungen zur intrazellulären Freisetzung von Nucleosidphosphaten
Structural and biochemical characterization of Siw14 : : a protein-tyrosine phosphatase fold that metabolizes inositol pyrophosphates
Activities, substrate specificity, and genetic interactions of fission yeast Siw14, a cysteinyl-phosphatase-type inositol pyrophosphatase
Synthesis of novel photocaged thiamine triphosphate prometabolites and investigations towards an efficient bidirectional synthesis of asymmetric dinucleoside polyphosphates
The 8th young faculty meeting – an active crowd attuned to modern challenges
Rapid synthesis of nucleoside triphosphates and analogues
Design of sensors for highly phosphorylated natural compounds
Novel shades of inositol pyrophosphates – in vitro and in cellulo evaluation of inositol pyrophosphate probes
Synthesis of bisdiphosphoinositol polyphosphate prometabolites
Investigations on the synthesis and degradation of polyphosphate in vitro and its correlation to magic spot nucleotides
Development of novel p-amidites and their application in the synthesis of the most densely phosphorylated compounds