{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cherilakkudy FH"],"funding":["NIGMS NIH HHS"],"pagination":["102779"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12439684"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(8)"],"pubmed_abstract":["ALKBH5 is one of only two known human non-heme Fe(II)/2-oxoglutarate-dependent oxygenases that catalyze the demethylation of N<sup>6</sup>-methyladenine (m<sup>6</sup>A) in single-stranded mRNA, underscoring its role in diverse cancers. Unlike its homolog, the fat mass and obesity-associated protein (FTO), which oxidizes m<sup>6</sup>A to a stable N<sup>6</sup>-hydroxymethyladenine (hm<sup>6</sup>A) intermediate, ALKBH5 demethylates m<sup>6</sup>A, yielding adenine and formaldehyde as products. Here, we integrate molecular dynamics simulations and quantum mechanics/molecular mechanics methods to elucidate ALKBH5's complete catalytic mechanism. Two post-hydroxylation pathways were evaluated: a proton transfer pathway and a Schiff base formation pathway, with the former emerging as the favor"],"journal":["Cell reports. Physical science"],"pubmed_title":["Revealing the catalytic mechanism of the Fe(II)/2-oxoglutarate-dependent human epigenetic modifying enzyme ALKBH5."],"pmcid":["PMC12439684"],"funding_grant_id":["R35 GM156437"],"pubmed_authors":["Waheed SO","Li D","Christov CZ","Cherilakkudy FH","Thomas MG","Venditti V","Karabencheva-Christova TG","Krishnan A","Varghese A","Schofield CJ"],"additional_accession":[]},"is_claimable":false,"name":"Revealing the catalytic mechanism of the Fe(II)/2-oxoglutarate-dependent human epigenetic modifying enzyme ALKBH5.","description":"ALKBH5 is one of only two known human non-heme Fe(II)/2-oxoglutarate-dependent oxygenases that catalyze the demethylation of N<sup>6</sup>-methyladenine (m<sup>6</sup>A) in single-stranded mRNA, underscoring its role in diverse cancers. Unlike its homolog, the fat mass and obesity-associated protein (FTO), which oxidizes m<sup>6</sup>A to a stable N<sup>6</sup>-hydroxymethyladenine (hm<sup>6</sup>A) intermediate, ALKBH5 demethylates m<sup>6</sup>A, yielding adenine and formaldehyde as products. Here, we integrate molecular dynamics simulations and quantum mechanics/molecular mechanics methods to elucidate ALKBH5's complete catalytic mechanism. Two post-hydroxylation pathways were evaluated: a proton transfer pathway and a Schiff base formation pathway, with the former emerging as the favor","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-06-01T06:21:59.503Z","creation":"2026-04-08T09:46:29.097Z"},"accession":"S-EPMC12439684","cross_references":{"pubmed":["40963693"],"doi":["10.1016/j.xcrp.2025.102779"]}}