Procollagen-lysine 5-dioxygenase (PLOD) (PLOD)

Procollagen-lysine 5-dioxygenase, commonly known as lysyl hydroxylase (PLOD), is a membrane-bound homodimeric enzyme located in the lumen of the endoplasmic reticulum (UniProt: P12744). It plays a critical role in the post-translational modification of collagen by catalyzing the hydroxylation of specific lysine residues to hydroxylysine, a process requiring iron, 2-oxoglutarate, oxygen, and ascorbate (Gjaltema & Bank, 2017). These hydroxylysine residues are essential for the formation of stable intermolecular cross-links that provide tensile strength to collagen fibers in the extracellular matrix. There are three human isoforms (PLOD1, PLOD2, and PLOD3), each with distinct tissue distributions and roles; for example, PLOD2 is specifically involved in the hydroxylation of telopeptide lysines (PubMed: 28233332). Dysregulation of these enzymes is linked to various pathologies, including Ehlers-Danlos syndrome (PLOD1) and Bruck syndrome (PLOD2). In oncology, PLOD2 overexpression is associated with increased collagen stiffness and cancer metastasis, making it a significant therapeutic target for anti-fibrotic and anti-metastatic drug development (Qi & Xu, 2018). While minoxidil has been identified as a non-specific inhibitor, current research focuses on developing selective small-molecule inhibitors to modulate collagen architecture in disease states (PubChem: CID 4201).

Other names

Lysyl hydroxylaseLHProcollagen-lysine,2-oxoglutarate 5-dioxygenase

Inhibition of the enzymatic hydroxylation of lysine residues in procollagen chains, preventing the formation of stable collagen cross-links.