Procollagen lysyl hydroxylases and glycosyltransferases (LH, also known as procollagen lysyl‐2‐oxoglutarate dioxygenases (PLOD)) are essential biosynthesis enzymes present in all collagen‐containing organisms, from sponges to humans. Higher vertebrates present three separate PLOD genes encoding for distinct enzyme isoforms (LH1, LH2a/b, and LH3), sharing ∼70% amino acid sequence identity. The LH1 and LH2 isoforms exclusively display Fe2+, 2‐oxoglutarate‐dependent lysyl 5‐hydroxylase activity, whereas LH3 is a multifunctional enzyme, able to further catalyze the Mn2+‐dependent β‐(1,O)‐galactosylation and the subsequent α‐(1,2)‐glucosylation of 5‐hydroxylysines. Despite exclusive selectivity for lysine residues within collagenous polypeptides, little is known about the specificity of LH enzymes for different amino acid sequences in different collagen types: LH1 and LH3 isoforms act on collagen triple‐helical regions, whereas the LH2 isoform specifically hydroxylates collagen telopeptides, yet no consensus sequences, nor minimum sequence lengths, have been proposed as requirements for catalysis. Available crystal structures of full‐length human LH3 show an elongated homodimeric quaternary structure, with three aligned domains constituting each enzyme's polypeptide: the N‐terminal glycosyltransferase (GT) domain, a central noncatalytic accessory (AC) domain, and a C‐terminal lysyl hydroxylase (LH) domain. Dimerization occurs in the C‐terminal domain, in proximity to the LH catalytic site. Dimerization is indeed essential for LH activity, but is dispensable for the glycosyltransferase activities of LH3.

Full‐Length Human Collagen Lysyl Hydroxylases

Scietti, Luigi
Writing – Original Draft Preparation
;
Forneris, Federico
Writing – Review & Editing
2020-01-01

Abstract

Procollagen lysyl hydroxylases and glycosyltransferases (LH, also known as procollagen lysyl‐2‐oxoglutarate dioxygenases (PLOD)) are essential biosynthesis enzymes present in all collagen‐containing organisms, from sponges to humans. Higher vertebrates present three separate PLOD genes encoding for distinct enzyme isoforms (LH1, LH2a/b, and LH3), sharing ∼70% amino acid sequence identity. The LH1 and LH2 isoforms exclusively display Fe2+, 2‐oxoglutarate‐dependent lysyl 5‐hydroxylase activity, whereas LH3 is a multifunctional enzyme, able to further catalyze the Mn2+‐dependent β‐(1,O)‐galactosylation and the subsequent α‐(1,2)‐glucosylation of 5‐hydroxylysines. Despite exclusive selectivity for lysine residues within collagenous polypeptides, little is known about the specificity of LH enzymes for different amino acid sequences in different collagen types: LH1 and LH3 isoforms act on collagen triple‐helical regions, whereas the LH2 isoform specifically hydroxylates collagen telopeptides, yet no consensus sequences, nor minimum sequence lengths, have been proposed as requirements for catalysis. Available crystal structures of full‐length human LH3 show an elongated homodimeric quaternary structure, with three aligned domains constituting each enzyme's polypeptide: the N‐terminal glycosyltransferase (GT) domain, a central noncatalytic accessory (AC) domain, and a C‐terminal lysyl hydroxylase (LH) domain. Dimerization occurs in the C‐terminal domain, in proximity to the LH catalytic site. Dimerization is indeed essential for LH activity, but is dispensable for the glycosyltransferase activities of LH3.
2020
9781119951438
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1360894
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact