6R77

Crystal structure of trans-3-Hydroxy-L-proline dehydratase in complex with substrate - closed conformation

Summary for 6R77

• Entry DOI: 10.2210/pdb6r77/pdb
• Descriptor: Proline racemase, 3-HYDROXYPROLINE (3 entities in total)
• Functional Keywords: trans-3-hydroxy-l-proline dehydratase, lyase, hydro-lyase, hydroxyproline metabolism
• Biological source: Thermococcus litoralis
• Total number of polymer chains: 2
• Total formula weight: 83613.59

Authors

Ferraris, D.M.,Miggiano, R.,Rizzi, M. (deposition date: 2019-03-28, release date: 2019-07-03, Last modification date: 2024-01-24)

Primary citation

Ferraris, D.M.,Miggiano, R.,Watanabe, S.,Rizzi, M.
Structure of Thermococcus litoralis trans-3-hydroxy-l-proline dehydratase in the free and substrate-complexed form.
Biochem.Biophys.Res.Commun., 516:189-195, 2019

PubMed Abstract: Hydroxyprolines (Hyp) are non-standard amino acids derived from the post-translational modification of proteins by prolyl hydroxylase enzymes. Some plants and bacteria produce Hyp, and the isomers trans-3-Hydroxy-l-proline (T3LHyp) and trans-4-Hydroxy-l-proline (T4LHyp) are major components of mammalian collagen. While T4LHyp is metabolised following distinct degradative pathways in mammals and bacteria, T3LHyp metabolic pathway is conserved in bacteria, plants and mammals, and involves a T3LHyp dehydratase (T3LHypD) in the first degradation step. We report here the crystal structure of T3LHypD from the archaea Thermococcus litoralis in the free and substrate-complexed form. The model shows an "open" and a "closed" conformation depending on the presence (or absence) of the substrate in the catalytic site and allows the mapping of the residues involved in ligand recognition. Moreover, the structure highlights the presence of a water molecule interacting with the hydroxy group of the substrate and potentially involved in catalysis. The structure here reported is the first of its family to be elucidated, and represents a valid model for rationalising the substrate specificity and catalysis of T3LHyp dehydratases.

PubMed: 31208721
DOI: 10.1016/j.bbrc.2019.06.021

Experimental method

X-RAY DIFFRACTION (2 Å)