Human iron(II) and 2-oxoglutarate-dependent prolyl and lysyl hydroxylases (Fe(II)/2-OG hydroxylases)

Human iron(II) and 2-oxoglutarate (2-OG)-dependent prolyl and lysyl hydroxylases are a superfamily of enzymes that catalyze the hydroxylation of specific proline or lysine residues in target proteins, such as Hypoxia-Inducible Factor (HIF) and collagen. These enzymes require Fe(II), 2-oxoglutarate, and molecular oxygen as co-substrates, making them critical sensors of cellular oxygen levels and metabolic state (Source: PMID: 21390221, UniProt). The prolyl hydroxylase domain (PHD) enzymes (EGLN1-3) regulate the stability of HIF-alpha, marking it for proteasomal degradation under normoxic conditions; their inhibition is a primary therapeutic strategy for treating anemia associated with chronic kidney disease (Source: PMID: 30643214). Additionally, lysyl hydroxylases (PLOD1-3) and prolyl 4-hydroxylases (P4HA1-3) are essential for the proper folding and cross-linking of collagen, making them significant targets in the study of fibrosis and cancer metastasis (Source: PMID: 31110015). Pharmacological modulation of these enzymes typically involves small-molecule inhibitors that compete with 2-oxoglutarate or chelate the active-site iron, offering a pathway to treat diverse conditions ranging from hematological disorders to fibroproliferative diseases.

Other names

2-oxoglutarate-dependent dioxygenases2-OGDDsHIF prolyl hydroxylasesProcollagen-proline dioxygenasesProcollagen-lysine dioxygenasesEGLN enzymesPLOD enzymes

Inhibition of prolyl hydroxylase domain (PHD) enzymes to stabilize Hypoxia-Inducible Factor (HIF), leading to increased erythropoietin production and erythropoiesis; or inhibition of collagen-modifying hydroxylases to prevent pathological fibrosis.