Structural studies on human 2-oxoglutarate dependent oxygenases.
2-Oxoglutarate and ferrous iron-dependent oxygenases have emerged as an important family of human enzymes that catalyse hydroxylations and related demethylation reactions. Their substrates in humans include proteins, nucleic acids, lipids and small molecules. They play roles in collagen biosynthesis, hypoxic sensing, regulation of gene expression and lipid biosynthesis/metabolism. Structural analyses, principally employing crystallography, have revealed that all of these oxygenases possess a double-stranded β-helix core fold that supports a highly conserved triad of iron binding residues and a less well conserved 2-oxoglutarate co-substrate binding site. The 2-oxoglutarate binds to the iron in a bidentate manner via its 1-carboxylate and 2-oxo groups. The primary substrate binding elements are more variable and can involve mobile elements.
McDonough
Michael A
MA
Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford OX1 3TA, UK.
Loenarz
Christoph
C
Chowdhury
Rasheduzzaman
R
Clifton
Ian J
IJ
Schofield
Christopher J
CJ
D000818:Animals; D055162:Biocatalysis; D005227:Fatty Acids / Q000096:biosynthesis; D006801:Humans; D006900:Hydroxylation; D007656:Ketoglutaric Acids / Q000378:metabolism*; D009696:Nucleic Acids / Q000378:metabolism; D010105:Oxygenases / Q000737:chemistry* / Q000378:metabolism*
D005227:Fatty Acids; D007656:Ketoglutaric Acids; D009696:Nucleic Acids; D010105:Oxygenases