{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sudhamalla B"],"funding":["University of Pittsburgh","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["10263-10269"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6400064"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["140(32)"],"pubmed_abstract":["Ten-eleven translocation (TET) enzymes employ O<sub>2</sub>, earth-abundant iron, and 2-ketoglutarate (2KG) to perform iterative C-H oxidation of 5-methylcytosine in DNA to control expression of the mammalian genome. Given that more than 60 such C-H oxygenases are present in humans, determining context-dependent functions of each of these enzymes is a pivotal challenge. In an effort to tackle the problem, we developed analogue-sensitive TET enzymes to perturb the activity of a specific member. We rationally engineered the TET2-2KG interface to develop TET2 variants with an expanded active site that can be specifically inhibited by the N-oxalylglycine (NOG) derivatives carrying a complementary steric \"bump\". Herein, we describe the identification and engineering of a bulky gatekeeper residu"],"journal":["Journal of the American Chemical Society"],"pubmed_title":["Complementary Steric Engineering at the Protein-Ligand Interface for Analogue-Sensitive TET Oxygenases."],"pmcid":["PMC6400064"],"funding_grant_id":["R01GM123234","R01 GM123234"],"pubmed_authors":["Kavoosi S","Snyder V","Wang S","Islam K","Sudhamalla B","Arora S"],"additional_accession":[]},"is_claimable":false,"name":"Complementary Steric Engineering at the Protein-Ligand Interface for Analogue-Sensitive TET Oxygenases.","description":"Ten-eleven translocation (TET) enzymes employ O<sub>2</sub>, earth-abundant iron, and 2-ketoglutarate (2KG) to perform iterative C-H oxidation of 5-methylcytosine in DNA to control expression of the mammalian genome. Given that more than 60 such C-H oxygenases are present in humans, determining context-dependent functions of each of these enzymes is a pivotal challenge. In an effort to tackle the problem, we developed analogue-sensitive TET enzymes to perturb the activity of a specific member. We rationally engineered the TET2-2KG interface to develop TET2 variants with an expanded active site that can be specifically inhibited by the N-oxalylglycine (NOG) derivatives carrying a complementary steric \"bump\". Herein, we describe the identification and engineering of a bulky gatekeeper residu","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Aug","modification":"2026-05-05T06:28:00.586Z","creation":"2025-05-29T20:01:53.177Z"},"accession":"S-EPMC6400064","cross_references":{"pubmed":["30028600"],"doi":["10.1021/jacs.8b05283"]}}