{"entity": "researcher", "timestamp": "2026-08-22T06:57:40.417Z", "family": "Hengge", "given": "Alvan C", "initials": "AC", "orcid": "0000-0002-5696-2087", "affiliations": ["Department of Chemistry and Biochemistry, Utah State University, Logan, Utah 84322-0300, United States."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/43fb9bec035e46c4a63263aded78a78b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/43fb9bec035e46c4a63263aded78a78b"}}, "publications": [{"entity": "publication", "iuid": "5b39a25a92404a84adf025ab9cb308b5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5b39a25a92404a84adf025ab9cb308b5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5b39a25a92404a84adf025ab9cb308b5"}}, "title": "Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases.", "authors": [{"family": "Shen", "given": "Ruidan", "initials": "R"}, {"family": "Crean", "given": "Rory M", "initials": "RM"}, {"family": "Olsen", "given": "Keith J", "initials": "KJ"}, {"family": "Corbella", "given": "Marina", "initials": "M", "orcid": "0000-0001-9209-868X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/53c414fb66534c3cbf91d3a3de055196.json"}}, {"family": "Calixto", "given": "Ana R", "initials": "AR"}, {"family": "Richan", "given": "Teisha", "initials": "T"}, {"family": "Brand\u00e3o", "given": "Tiago A S", "initials": "TAS"}, {"family": "Berry", "given": "Ryan D", "initials": "RD"}, {"family": "Tolman", "given": "Alex", "initials": "A"}, {"family": "Loria", "given": "J Patrick", "initials": "JP"}, {"family": "Johnson", "given": "Sean J", "initials": "SJ", "orcid": "0000-0001-7992-2494", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4229ef82708c44c5bb6a3fabf913c44b.json"}}, {"family": "Kamerlin", "given": "Shina C L", "initials": "SCL", "orcid": "0000-0002-3190-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4540c85432f4cdf952b0ef7cfe1d875.json"}}, {"family": "Hengge", "given": "Alvan C", "initials": "AC", "orcid": "0000-0002-5696-2087", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43fb9bec035e46c4a63263aded78a78b.json"}}], "type": "journal article", "published": "2022-11-23", "journal": {"title": "Chem Sci", "issn": "2041-6520", "volume": "13", "issue": "45", "pages": "13524-13540", "issn-l": null}, "abstract": "Protein tyrosine phosphatases (PTPs) possess a conserved mobile catalytic loop, the WPD-loop, which brings an aspartic acid into the active site where it acts as an acid/base catalyst. Prior experimental and computational studies, focused on the human enzyme PTP1B and the PTP from Yersinia pestis, YopH, suggested that loop conformational dynamics are important in regulating both catalysis and evolvability. We have generated a chimeric protein in which the WPD-loop of YopH is transposed into PTP1B, and eight chimeras that systematically restored the loop sequence back to native PTP1B. Of these, four chimeras were soluble and were subjected to detailed biochemical and structural characterization, and a computational analysis of their WPD-loop dynamics. The chimeras maintain backbone structural integrity, with somewhat slower rates than either wild-type parent, and show differences in the pH dependency of catalysis, and changes in the effect of Mg2+. The chimeric proteins' WPD-loops differ significantly in their relative stability and rigidity. The time required for interconversion, coupled with electrostatic effects revealed by simulations, likely accounts for the activity differences between chimeras, and relative to the native enzymes. Our results further the understanding of connections between enzyme activity and the dynamics of catalytically important groups, particularly the effects of non-catalytic residues on key conformational equilibria.", "doi": "10.1039/d2sc04135a", "pmid": "36507179", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9682893"}, {"db": "pii", "key": "d2sc04135a"}], "notes": [], "created": "2026-08-21T11:58:06.696Z", "modified": "2026-08-21T11:58:06.822Z"}, {"entity": "publication", "iuid": "519b285dd47440b999323898a773c73b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/519b285dd47440b999323898a773c73b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/519b285dd47440b999323898a773c73b"}}, "title": "Correction to \"Loop Dynamics and Enzyme Catalysis in Protein Tyrosine Phosphatases\".", "authors": [{"family": "Crean", "given": "Rory M", "initials": "RM"}, {"family": "Biler", "given": "Michal", "initials": "M", "orcid": "0000-0003-3809-6928", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4e9f22f57e441cb9028720d6a4b2bfa.json"}}, {"family": "Corbella", "given": "Marina", "initials": "M", "orcid": "0000-0001-9209-868X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/53c414fb66534c3cbf91d3a3de055196.json"}}, {"family": "Calixto", "given": "Ana R", "initials": "AR", "orcid": "0000-0002-1123-0413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/91f7bbeb7f3245449679931f97d21eb8.json"}}, {"family": "van der Kamp", "given": "Marc W", "initials": "MW", "orcid": "0000-0002-8060-3359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9e09f39776374aeca06c0a767d62bfac.json"}}, {"family": "Hengge", "given": "Alvan C", "initials": "AC", "orcid": "0000-0002-5696-2087", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43fb9bec035e46c4a63263aded78a78b.json"}}, {"family": "Kamerlin", "given": "Shina C L", "initials": "SCL", "orcid": "0000-0002-3190-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4540c85432f4cdf952b0ef7cfe1d875.json"}}], "type": "published erratum", "published": "2022-06-08", "journal": {"title": "Journal of the American Chemical Society", "issn": "1520-5126", "volume": "144", "issue": "22", "pages": "10091-10093", "issn-l": "0002-7863"}, "abstract": null, "doi": "10.1021/jacs.2c04624", "pmid": "35609280", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11027752"}], "notes": [], "created": "2026-08-21T11:37:56.469Z", "modified": "2026-08-21T11:37:56.639Z"}, {"entity": "publication", "iuid": "7b87917c4e4f4d47993d8f528607accc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7b87917c4e4f4d47993d8f528607accc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7b87917c4e4f4d47993d8f528607accc"}}, "title": "Loop Dynamics and Enzyme Catalysis in Protein Tyrosine Phosphatases.", "authors": [{"family": "Crean", "given": "Rory M", "initials": "RM"}, {"family": "Biler", "given": "Michal", "initials": "M"}, {"family": "van der Kamp", "given": "Marc W", "initials": "MW", "orcid": "0000-0002-8060-3359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9e09f39776374aeca06c0a767d62bfac.json"}}, {"family": "Hengge", "given": "Alvan C", "initials": "AC", "orcid": "0000-0002-5696-2087", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43fb9bec035e46c4a63263aded78a78b.json"}}, {"family": "Kamerlin", "given": "Shina C L", "initials": "SCL", "orcid": "0000-0002-3190-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4540c85432f4cdf952b0ef7cfe1d875.json"}}], "type": "journal article", "published": "2021-03-17", "journal": {"title": "Journal of the American Chemical Society", "issn": "1520-5126", "volume": "143", "issue": "10", "pages": "3830-3845", "issn-l": "0002-7863"}, "abstract": "Protein tyrosine phosphatases (PTPs) play an important role in cellular signaling and have been implicated in human cancers, diabetes, and obesity. Despite shared catalytic mechanisms and transition states for the chemical steps of catalysis, catalytic rates within the PTP family vary over several orders of magnitude. These rate differences have been implied to arise from differing conformational dynamics of the closure of a protein loop, the WPD-loop, which carries a catalytically critical residue. The present work reports computational studies of the human protein tyrosine phosphatase 1B (PTP1B) and YopH from Yersinia pestis, for which NMR has demonstrated a link between their respective rates of WPD-loop motion and catalysis rates, which differ by an order of magnitude. We have performed detailed structural analysis, both conventional and enhanced sampling simulations of their loop dynamics, as well as empirical valence bond simulations of the chemical step of catalysis. These analyses revealed the key residues and structural features responsible for these differences, as well as the residues and pathways that facilitate allosteric communication in these enzymes. Curiously, our wild-type YopH simulations also identify a catalytically incompetent hyper-open conformation of its WPD-loop, sampled as a rare event, previously only experimentally observed in YopH-based chimeras. The effect of differences within the WPD-loop and its neighboring loops on the modulation of loop dynamics, as revealed in this work, may provide a facile means for the family of PTP enzymes to respond to environmental changes and regulate their catalytic activities.", "doi": "10.1021/jacs.0c11806", "pmid": "33661624", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8031367"}], "notes": [], "created": "2026-08-21T11:37:51.587Z", "modified": "2026-08-21T11:37:51.656Z"}]}