{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Friedman AJ"],"funding":["NIGMS NIH HHS"],"pubmed_abstract":["Protein tyrosine phosphatases (PTPs) are emerging drug targets for many diseases, including type 2 diabetes, obesity, and cancer. However, a high degree of structural similarity between the catalytic domains of these enzymes has made the development of selective pharmacological inhibitors an enormous challenge. Our previous research uncovered two unfunctionalized terpenoid inhibitors that selectively inhibit PTP1B over TCPTP, two PTPs with high sequence conservation. Here, we use molecular modeling with experimental validation to study the molecular basis of this unusual selectivity. Molecular dynamics (MD) simulations indicate that PTP1B and TCPTP contain a conserved h-bond network that connects the active site to a distal allosteric pocket; this network stabilizes the closed conformation"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.04.17.537234"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10153121"],"repository":["biostudies-literature"],"pubmed_title":["A biophysical rationale for the selective inhibition of PTP1B over TCPTP by nonpolar terpenoids."],"pmcid":["PMC10153121"],"funding_grant_id":["R35 GM143089"],"pubmed_authors":["Shirts MR","Donovan GW","Fox JM","Friedman AJ","Kramer L","Padgette HM","Liechty ET"],"additional_accession":[]},"is_claimable":false,"name":"A biophysical rationale for the selective inhibition of PTP1B over TCPTP by nonpolar terpenoids.","description":"Protein tyrosine phosphatases (PTPs) are emerging drug targets for many diseases, including type 2 diabetes, obesity, and cancer. However, a high degree of structural similarity between the catalytic domains of these enzymes has made the development of selective pharmacological inhibitors an enormous challenge. Our previous research uncovered two unfunctionalized terpenoid inhibitors that selectively inhibit PTP1B over TCPTP, two PTPs with high sequence conservation. Here, we use molecular modeling with experimental validation to study the molecular basis of this unusual selectivity. Molecular dynamics (MD) simulations indicate that PTP1B and TCPTP contain a conserved h-bond network that connects the active site to a distal allosteric pocket; this network stabilizes the closed conformation","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2026-04-08T13:59:44.541Z","creation":"2026-04-08T03:24:25.834Z"},"accession":"S-EPMC10153121","cross_references":{"pubmed":["37131728"],"doi":["10.1101/2023.04.17.537234"]}}