Journal article

Human oxygen sensing may have origins in prokaryotic elongation factor Tu prolyl-hydroxylation

John S Scotti, Ivanhoe KH Leung, Wei Ge, Michael A Bentley, Jordi Paps, Holger B Kramer, Joongoo Lee, WeiShen Aik, Hwanho Choi, Steinar M Paulsen, Lesley AH Bowman, Nikita D Loik, Shoichiro Horita, Chia-hua Ho, Nadia J Kershaw, Christoph M Tang, Timothy DW Claridge, Gail M Preston, Michael A McDonough, Christopher J Schofield

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2014

Abstract

The roles of 2-oxoglutarate (2OG)-dependent prolyl-hydroxylases in eukaryotes include collagen stabilization, hypoxia sensing, and translational regulation. The hypoxia-inducible factor (HIF) sensing system is conserved in animals, but not in other organisms. However, bioinformatics imply that 2OG-dependent prolyl-hydroxylases (PHDs) homologous to those acting as sensing components for the HIF system in animals occur in prokaryotes. We report cellular, biochemical, and crystallographic analyses revealing that Pseudomonas prolyl-hydroxylase domain containing protein (PPHD) contain a 2OG oxygenase related in structure and function to the animal PHDs. A Pseudomonas aeruginosa PPHD knockout muta..

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Grants

Awarded by Biotechnology and Biological Sciences Research Council


Awarded by British Heart Foundation


Awarded by Engineering and Physical Sciences Research Council


Funding Acknowledgements

We thank the Diamond Macromolecular Crystallography beamline staff for technical support; Dr. Christoph Loenarz and Prof. Peter J. Ratcliffe for helpful discussion; and the Rhodes Trust (J.S.S.), the British Heart Foundation (I.K.H.L.), the Wellcome Trust, the European Research Council, the Japan Society for the Promotion of Science (S.H.), and the Biotechnology and Biological Sciences Research Council for financial support.