Pro-metastatic collagen lysyl hydroxylase dimer assemblies stabilized by Fe²⁺-binding.

ABSTRACT: Collagen lysyl hydroxylases (LH1-3) are Fe²⁺- and 2-oxoglutarate (2-OG)-dependent oxygenases that maintain extracellular matrix homeostasis. High LH2 levels cause stable collagen cross-link accumulations that promote fibrosis and cancer progression. However, developing LH antagonists will require structural insights. Here, we report a 2 Å crystal structure and X-ray scattering on dimer assemblies for the LH domain of L230 in Acanthamoeba polyphaga mimivirus. Loop residues in the double-stranded β-helix core generate a tail-to-tail dimer. A stabilizing hydrophobic leucine locks into an aromatic tyrosine-pocket on the opposite subunit. An active site triad coordinates Fe²⁺. The two active sites flank a deep surface cleft that suggest dimerization creates a collagen-bind

SUBMITTER: Guo HF 

PROVIDER: S-EPMC5802723 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature