Structure and Mechanism of a Viral Collagen Prolyl Hydroxylase

J. E. Longbotham, C. Levy, L. O. Johannissen, H. Tarhonskaya, S. Jiang, C. Loenarz, E. Flashman, S. Hay, C. J. Schofield, N. S. Scrutton

Research output: Contribution to journalArticlepeer-review


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 beta-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.
Original languageEnglish
Pages (from-to)6093-6105
Number of pages13
Issue number39
Publication statusPublished - 2015


  • Amino Acid Motifs Catalytic Domain Crystallography, X-Ray Iron/*chemistry Phycodnaviridae/*enzymology Prolyl Hydroxylases/*chemistry Viral Proteins/*chemistry


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