ArticleJournal of molecular biology2011
Visualizing active-site dynamics in single crystals of HePTP: opening of the WPD loop involves coordinated movement of the E loop.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
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- Loop dynamics, allostery, and function in protein tyrosine phosphatases: insights from molecular simulations.Biochemical Society transactions · 2026Review
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- Orchestrating function: Concerted dynamics, allostery, and catalysis in protein tyrosine phosphatases.Current opinion in structural biology · 2025Review
- Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction.Protein science : a publication of the Protein Society · 2025Article
- An expanded trove of fragment-bound structures for the allosteric enzyme PTP1B from computational reanalysis of large-scale crystallographic data.Structure (London, England : 1993) · 2024Article
- Pushed to extremes: distinct effects of high temperature versus pressure on the structure of STEP.Communications biology · 2024Article
- An expanded view of ligandability in the allosteric enzyme PTP1B from computational reanalysis of large-scale crystallographic data.bioRxiv : the preprint server for biology · 2024Article
- Pushed to extremes: distinct effects of high temperature vs. pressure on the structure of an atypical phosphatase.bioRxiv : the preprint server for biology · 2023Article
- Computational Methods in Cooperation with Experimental Approaches to Design Protein Tyrosine Phosphatase 1B Inhibitors in Type 2 Diabetes Drug Design: A Review of the Achievements of This Century.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The catalytic activity of TCPTP is auto-regulated by its intrinsically disordered tail and activated by Integrin alpha-1.Nature communications · 2022Article
- A New Paradigm for KIM-PTP Drug Discovery: Identification of Allosteric Sites with Potential for Selective Inhibition Using Virtual Screening and LEI Analysis.International journal of molecular sciences · 2021Article
- Protein Tyrosine Phosphatases: A new paradigm in an old signaling system?Advances in cancer research · 2021Review
- Article
- Cooperative dynamics across distinct structural elements regulate PTP1B activity.The Journal of biological chemistry · 2020Article
- The KIM-family protein-tyrosine phosphatases use distinct reversible oxidation intermediates: Intramolecular or intermolecular disulfide bond formation.The Journal of biological chemistry · 2017Article
- SHP family protein tyrosine phosphatases adopt canonical active-site conformations in the apo and phosphate-bound states.Protein and peptide letters · 2013Article
- Frequency response of a protein to local conformational perturbations.PLoS computational biology · 2013Article
- Protein tyrosine phosphatases: structure, function, and implication in human disease.Methods in molecular biology (Clifton, N.J.) · 2013Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphotyrosine hydrolysis by protein tyrosine phosphatases (PTPs) involves substrate binding by the PTP loop and closure over the active site by the WPD loop. The E loop, located immediately adjacent to the PTP and WPD loops, is conserved among human PTPs in both sequence and structure, yet the role of this loop in substrate binding and catalysis is comparatively unexplored. Hematopoietic PTP (HePTP) is a member of the kinase interaction motif (KIM) PTP family. Compared to other PTPs, KIM-PTPs have E loops that are unique in both sequence and structure. In order to understand the role of the E loop in the transition between the closed state and the open state of HePTP, we identified a novel crystal form of HePTP that allowed the closed-state-to-open-state transition to be observed within a single crystal form. These structures, which include the first structure of the HePTP open state, show that the WPD loop adopts an 'atypically open' conformation and, importantly, that ligands can be exchanged at the active site, which is critical for HePTP inhibitor development. These structures also show that tetrahedral oxyanions bind at a novel secondary site and function to coordinate the PTP, WPD, and E loops. Finally, using both structural and kinetic data, we reveal a novel role for E-loop residue Lys182 in enhancing HePTP catalytic activity through its interaction with Asp236 of the WPD loop, providing the first evidence for the coordinated dynamics of the WPD and E loops in the catalytic cycle, which, as we show, is relevant to multiple PTP families.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.