Studies on non-haem ferrous-dependent oxygenases and oxidases

Barlow, John N.; Baldwin, Jack E.; Clifton, I.J.; Gibson, Eddie; Hensgens, Charles M.H.; Hajdu, János; Hara, Takehisa; Hassan, Abby; John, P. S.; Lloyd, Matthew D.; Roach, Peter L.; Prescott, Andy G.; Robinson, John K.; Schofield, Christopher J.

doi:10.1042/bst0250086

Cited by 7 publications

(5 citation statements)

References 16 publications

(25 reference statements)

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“…It has been proposed that the ferrous iron dependent oxygenases may have evolved as a response to the advent of photosynthetically produced oxygen, possibly from precursors that used relatively bioavailable iron (comparable to eg, zinc) ions, predominantly in non-redox processes. 68 , 69 The widespread occurrence of 2OG oxygenases in prokaryotes, coupled with their close relationship with two TCA cycle intermediates (2OG and succinate), suggests they may have early origins. The discovery that 2OG oxygenases play key roles in hypoxia sensing in higher animals was therefore of interest from a broad evolutionary perspective.…”

Section: Discussionmentioning

confidence: 99%

Born to sense: biophysical analyses of the oxygen sensing prolyl hydroxylase from the simplest animal <em>Trichoplax adhaerens</em>

Lippl¹,

Boleininger²,

McDonough³

et al. 2018

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BackgroundIn humans and other animals, the chronic hypoxic response is mediated by hypoxia inducible transcription factors (HIFs) which regulate the expression of genes that counteract the effects of limiting oxygen. Prolyl hydroxylases (PHDs) act as hypoxia sensors for the HIF system in organisms ranging from humans to the simplest animal Trichoplax adhaerens.MethodsWe report structural and biochemical studies on the T. adhaerens HIF prolyl hydroxylase (TaPHD) that inform about the evolution of hypoxia sensing in animals.ResultsHigh resolution crystal structures (≤1.3 Å) of TaPHD, with and without its HIFα substrate, reveal remarkable conservation of key active site elements between T. adhaerens and human PHDs, which also manifest in kinetic comparisons.ConclusionConserved structural features of TaPHD and human PHDs include those apparently enabling the slow binding/reaction of oxygen with the active site Fe(II), the formation of a stable 2-oxoglutarate complex, and a stereoelectronically promoted change in conformation of the hydroxylated proline-residue. Comparison of substrate selectivity between the human PHDs and TaPHD provides insights into the selectivity determinants of HIF binding by the PHDs, and into the evolution of the multiple HIFs and PHDs present in higher animals.

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Section: Discussionmentioning

confidence: 99%

Born to sense: biophysical analyses of the oxygen sensing prolyl hydroxylase from the simplest animal <em>Trichoplax adhaerens</em>

Lippl¹,

Boleininger²,

McDonough³

et al. 2018

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“…The GA dioxygenases are often multifunctional with a broad substrate speci®city, resulting in many side reactions and the numerous GAs found in higher plants (Lange and Graebe 1993;Hedden and Kamiya 1997). These enzymes belong to the recently identi®ed family of non-haem iron-containing oxygenases and oxidases (Prescott 1993;De Carolis and De Luca 1994;Prescott and John 1996;Barlow et al 1997). From GA 12 -aldehyde, a principal pathway to the GA plant hormones can be drawn that involves just three GA dioxygenases, 7-oxidase, 20-oxidase and 3b-hydroxylase (Fig.…”

Section: General Principles Of Gibberellin Biosynthetic Pathwaysmentioning

confidence: 98%

Molecular biology of gibberellin synthesis

Lange¹

1998

Planta

100

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“…Several general reviews on these enzymes have previously appeared. [1][2][3][4][5][6] There are also reviews on specific enzymes including the following: those involved in penicillin, cephalosporin and cephamycin biosynthesis; 7,8 clavam biosynthesis; 9 those of plant enzymes; 10-12 ethylene biosynthesis; 13,14 carnitine biosynthesis; 15 and collagen biosynthesis. 16 Many of these enzymes function in pathways which have medical, pharmaceutical or agricultural significance, and several of them have been implicated in disease states including the following: prolyl hydroxylase (P4H) in alcoholic liver cirrhosis; 17,18 lysyl hydroxylase (LH) in Ehlers-Danlos syndrome type VI; 18 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) in tyrosinaemia type III 19 and hawkinsinuria; 20,21 phytanoyl-CoA hydroxylase (PAHX) in Refsum's disease.…”

Section: Introductionmentioning

confidence: 99%