Procollagen-lysine,2-oxoglutarate 5-dioxygenase (PLOD) (PLOD)

Procollagen-lysine,2-oxoglutarate 5-dioxygenase (PLOD), also known as collagen lysyl hydroxylase, is a homodimeric enzyme residing in the endoplasmic reticulum that plays a pivotal role in collagen biosynthesis [UniProt: P12187]. It catalyzes the hydroxylation of specific lysine residues in procollagen, which is a prerequisite for the formation of hydroxylysine-linked cross-links that provide tensile strength to the extracellular matrix [PubMed: 29456134]. There are three human isoforms: PLOD1, PLOD2, and PLOD3, each with distinct roles; for instance, PLOD1 is essential for skin and bone collagen, while PLOD2 is critical for the stable cross-linking of collagen in hard tissues and fibrotic lesions [UniProt: O00468]. Mutations in PLOD1 lead to Ehlers-Danlos syndrome type VI, characterized by severe muscle hypotonia and joint laxity, whereas PLOD2 overexpression is a hallmark of various cancers and fibrotic diseases [OMIM: 225400]. In oncology, PLOD2-mediated collagen remodeling promotes a stiff microenvironment that facilitates tumor cell migration and metastasis [PubMed: 23303905]. While minoxidil has been identified as an inhibitor of lysyl hydroxylase in fibroblasts, current research is focused on developing highly selective small-molecule inhibitors to treat fibrosis and prevent cancer progression [PubMed: 2112454].

Other names

Collagen lysyl hydroxylaseLysyl hydroxylaseLHProcollagen-lysine 5-dioxygenase

Inhibition of the enzymatic activity of lysyl hydroxylase to prevent the formation of hydroxylysine-linked collagen cross-links, thereby reducing collagen stability and extracellular matrix stiffness.