InterPro domain: IPR044862

Mammalian prolyl 4-hydroxylase alpha catalyses the posttranslational formation of 4-hydroxyproline in -xaa-pro-gly-sequences in collagens and other proteins. Prokaryotic enzymes might catalyse hydroxylation of antibiotic peptides. These are 2-oxoglutarate-dependent dioxygenases, requiring 2-oxoglutarate and dioxygen as cosubstrates and ferrous iron as a cofactor [ 1 ].

This entry represents the Fe(2) 2-oxoglutarate dioxygenase domain found in prolyl 4-hydroxylase alpha subunit 1/2/3 from animals and related proteins such as PKHD-type hydroxylase YbiX from bacteria.

The iron 2OG dioxygenase domain has a conserved beta-barrel structure [ 2 ], which forms a double-stranded beta-helix core fold that forms the predominant class of the cupin superfamily ('cupa' means a small barrel in Latin) [ 3 ]. Two histidines and an aspartate residue catalytically bind a metal ion, in general iron but in some cases another metal, directly involved in catalysis. A conserved arginine or lysine residue further near the C-terminal part acts as the basic residue that interacts with the acidic substrate.

1. The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases. Genome Biol. 2, RESEARCH0007
2. Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2). Proc. Natl. Acad. Sci. U.S.A. 103, 9814-9
3. Cupins: the most functionally diverse protein superfamily? Phytochemistry 65, 7-17