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

Scotti, John S and Leung, Ivanhoe KH and Ge, Wei and Bentley, Michael A and Paps, Jordi and Kramer, Holger B and Lee, Joongoo and Aik, WeiShen and Choi, Hwanho and Paulsen, Steinar M and Bowman, Lesley AH and Loik, Nikita D and Horita, Shoichiro and Ho, Chia-hua and Kershaw, Nadia J and Tang, Christoph M and Claridge, Timothy DW and Preston, Gail M and McDonough, Michael A and Schofield, Christopher J (2014) 'Human oxygen sensing may have origins in prokaryotic elongation factor Tu prolyl-hydroxylation.' Proceedings of the National Academy of Sciences, 111 (37). pp. 13331-13336. ISSN 0027-8424

2014 Scotti---Paps Human oxygen sensing may have origins in prokaryotic EF Tu PNAS.pdf

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<jats:title>Significance</jats:title> <jats:p> The Fe(II)- and 2-oxoglutarate (2OG)-dependent hypoxia-inducible transcription factor prolyl-hydroxylases play a central role in human oxygen sensing and are related to other prolyl-hydroxylases involved in eukaryotic collagen biosynthesis and ribosomal modification. The finding that a PHD-related prolyl-hydroxylase in <jats:italic>Pseudomonas spp.</jats:italic> regulates pyocyanin biosynthesis supports prokaryotic origins for the eukaryotic prolyl-hydroxylases. The identification of the switch I loop of elongation factor Tu (EF-Tu) as a <jats:italic>Pseudomonas</jats:italic> prolyl-hydroxylase domain containing protein (PPHD) substrate provides evidence of roles for 2OG oxygenases in both translational and transcriptional regulation. A structure of the PPHD:EF-Tu complex, the first to the authors' knowledge of a 2OG oxygenase with its intact protein substrate, reveals that major conformational changes occur in both PPHD and EF-Tu and will be useful in the design of new prolyl-hydroxylase inhibitors. </jats:p>

Item Type: Article
Uncontrolled Keywords: Humans; Chlamydomonas reinhardtii; Pseudomonas putida; Oxygen; Peptide Elongation Factor Tu; Proline; Protein Structure, Secondary; Protein Structure, Tertiary; Substrate Specificity; Hydroxylation; Models, Molecular; Molecular Sequence Data; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 01 Oct 2015 09:24
Last Modified: 18 Aug 2022 10:43

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