5C5T

The crystal structure of viral collagen prolyl hydroxylase vCPH from Paramecium Bursaria Chlorella virus-1 - 2OG complex

Summary for 5C5T

• Entry DOI: 10.2210/pdb5c5t/pdb
• Descriptor: Prolyl 4-hydroxylase, 2-OXOGLUTARIC ACID, ZINC ION, ... (5 entities in total)
• Functional Keywords: dioxygenase, prolyl hydroxylase, oxidoreductase
• Biological source: Paramecium bursaria Chlorella virus 1 (PBCV-1)
• Total number of polymer chains: 2
• Total formula weight: 52214.62

Authors

Levy, C.W. (deposition date: 2015-06-22, release date: 2015-09-30, Last modification date: 2024-11-20)

Primary citation

Longbotham, J.E.,Levy, C.,Johannissen, L.O.,Tarhonskaya, H.,Jiang, S.,Loenarz, C.,Flashman, E.,Hay, S.,Schofield, C.J.,Scrutton, N.S.
Structure and Mechanism of a Viral Collagen Prolyl Hydroxylase.
Biochemistry, 54:6093-6105, 2015

PubMed Abstract: The Fe(II)- and 2-oxoglutarate (2-OG)-dependent dioxygenases comprise a large and diverse enzyme superfamily the members of which have multiple physiological roles. Despite this diversity, these enzymes share a common chemical mechanism and a core structural fold, a double-stranded β-helix (DSBH), as well as conserved active site residues. The prolyl hydroxylases are members of this large superfamily. Prolyl hydroxylases are involved in collagen biosynthesis and oxygen sensing in mammalian cells. Structural-mechanistic studies with prolyl hydroxylases have broader implications for understanding mechanisms in the Fe(II)- and 2-OG-dependent dioxygenase superfamily. Here, we describe crystal structures of an N-terminally truncated viral collagen prolyl hydroxylase (vCPH). The crystal structure shows that vCPH contains the conserved DSBH motif and iron binding active site residues of 2-OG oxygenases. Molecular dynamics simulations are used to delineate structural changes in vCPH upon binding its substrate. Kinetic investigations are used to report on reaction cycle intermediates and compare them to the closest homologues of vCPH. The study highlights the utility of vCPH as a model enzyme for broader mechanistic analysis of Fe(II)- and 2-OG-dependent dioxygenases, including those of biomedical interest.

PubMed: 26368022
DOI: 10.1021/acs.biochem.5b00789

Experimental method

X-RAY DIFFRACTION (1.598 Å)