Literature summary for 1.14.11.53 extracted from

Toh, J.; Crossley, S.; Bruemmer, K.; Ge, E.; He, D.; Iovan, D.; Chang, C.
Distinct RNA N-demethylation pathways catalyzed by nonheme iron ALKBH5 and FTO enzymes enable regulation of formaldehyde release rates (2020), Proc. Natl. Acad. Sci. USA, 117, 25284-25292 .

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Protein Variants

Protein Variants	Comment	Organism
K132Q	mutant furnishes the ALKBH5 enzyme with an m6A demethylation profile that resembles that of isoform FTO	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q6P6C2	isoform ALKBH5	-
Homo sapiens	Q9C0B1	-	-

Synonyms

Synonyms	Comment	Organism
FTO	-	Homo sapiens

General Information

General Information	Comment	Organism
metabolism	comparison of isoforms FTO and ALKBH5. FTO behaves like a classical nonheme Fe(II)-2OG-dependent dioxygenase by performing stepwise oxidation, whereas ALKBH5 catalyzes a unique direct 6-methyladenosine-to-adenosine conversion with rapid release of formaldehyde. A catalytic R130/K132/Y139 triad within ALKBH5 facilitates release of formaldehyde via an covalent-based demethylation mechanism with direct detection of a covalent intermediate. In a mechanistic model for ALKBH5, K132 promotes Schiff base formation on hm6A, which may then undergo subsequent nucleophilic attack by K132 or Y139. Y139 may alternatively play a role in nucleobase recognition via hydrogen bonding to the N6 nitrogen. Formation of a methylene bridge between K132 and Y139 is a probable intermediate prior to hydrolysis and may facilitate release of adeosine	Homo sapiens
metabolism	comparison of isoforms FTO and ALKBH5. FTO follows a traditional oxidative N-demethylation pathway to catalyze conversion of m6A to hm6A with subsequent slow release of adenosine and formaldehyde. FTO behaves like a classical nonheme Fe(II)-2OG-dependent dioxygenase by performing stepwise oxidation, whereas ALKBH5 catalyzes a unique direct 6-methyladenosine-to-adeosine conversion. FTO gives 6-hydroxymethyladenosine as a major product and 6-formyladenosine as a minorproduct	Homo sapiens

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Release 2023.1 (January 2023)