Fe(II)/alpha-ketoglutarate hydroxylases involved in nucleobase, nucleoside, nucleotide, and chromatin metabolism.
Fe(II)/alpha-ketoglutarate-dependent hydroxylases uniformly possess a double-stranded beta-helix fold with two conserved histidines and one carboxylate coordinating their mononuclear ferrous ions. Oxidative decomposition of the alpha-keto acid is proposed to generate a ferryl-oxo intermediate capable of hydroxylating unactivated carbon atoms in a myriad of substrates. This Perspective focuses on a subgroup of these enzymes that are involved in pyrimidine salvage, purine decomposition, nucleoside and nucleotide hydroxylation, DNA/RNA repair, and chromatin modification. The varied reaction schemes are presented, and selected structural and kinetic information is summarized.
Simmons
Jana M
JM
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA.
Müller
Tina A
TA
Hausinger
Robert P
RP
D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D049308:Dioxygenases / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008958:Models, Molecular; D009705:Nucleosides / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D011119:Polynucleotides / Q000378:metabolism
D002843:Chromatin; D005656:Fungal Proteins; D009705:Nucleosides; D009711:Nucleotides; D011119:Polynucleotides; D007501:Iron; D006899:Mixed Function Oxygenases; D049308:Dioxygenases; C503093:xanthine dioxygenase, Aspergillus nidulans; C023164:thymine, 2-oxoglutarate dioxygenase