The Carboxylation of Preprothrombin

Esnouf, M. P.; Gainey, A I; Hill, H. Allen O.; Thornalley, Paul J.

doi:10.1007/978-1-4612-5829-2_20

Cited by 4 publications

(4 citation statements)

References 14 publications

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“…Component C2 can also be attributed to a superoxide radical, despite a disagreement of aH γ for this species. 46 Component C3 can be attributed to a hydroxyl radical, which is expected to be present due to the well-known dismutation of DMPO-OOH into DMPO-OH. 45,47 Component C4 has typical features of a carbonbased radical but could not be attributed to any particular chemical species.…”

Section: Coelenterazine Oxidation Proceeds Via a Superoxide Radicalmentioning

confidence: 99%

Catalytic mechanism for Renilla-type luciferases

et al. 2023

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The widely used coelenterazine-powered Renilla luciferase was discovered over 40 years ago but the oxidative mechanism by which it generates blue photons remains unclear. Here we decipher Renillatype bioluminescence through crystallographic, spectroscopic, and computational experiments.Structures of ancestral and extant luciferases complexed with the substrate-like analogue azacoelenterazine or a reaction product were obtained, providing unprecedented snapshots of coelenterazine-to-coelenteramide oxidation. Bound coelenterazine adopts a Y-shaped conformation, enabling the deprotonated imidazopyrazinone component to attack O2 via a radical charge-transfer mechanism. A high emission intensity is secured by an aspartate from a conserved proton-relay system, which protonates the excited coelenteramide product. Another aspartate on the rim of the catalytic pocket fine-tunes the electronic state of coelenteramide and promotes the formation of the blue lightemitting phenolate anion. The results obtained also reveal structural features distinguishing flash-type from glow-type bioluminescence, providing insights that will guide the engineering of next-generation luciferase-luciferin pairs for ultrasensitive optical bioassays.

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Section: Coelenterazine Oxidation Proceeds Via a Superoxide Radicalmentioning

confidence: 99%

Catalytic mechanism for Renilla-type luciferases

et al. 2023

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“…The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.479090 doi: bioRxiv preprint also be attributed to a superoxide radical, despite a disagreement of aH γ for this species. 46 Component C3 can be attributed to a hydroxyl radical, which is expected to be present due to the well-known dismutation of DMPO-OOH into DMPO-OH. 45,47 Component C4 has typical features of a carbonbased radical but could not be attributed to any particular chemical species.…”

Section: Coelenterazine Oxidation Proceeds Via a Superoxide Radicalmentioning

confidence: 99%

A catalytic mechanism for Renilla-type bioluminescence

Schenkmayerova

Toul

Pluskal

et al. 2022

Preprint

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The widely used coelenterazine-powered Renilla luciferase was discovered over 40 years ago but the oxidative mechanism by which it generates blue photons remains unclear. Here we decipher Renilla-type bioluminescence through crystallographic, spectroscopic, and computational experiments. Structures of ancestral and extant luciferases complexed with the substrate-like analogue azacoelenterazine or a reaction product were obtained, providing unprecedented snapshots of coelenterazine-to-coelenteramide oxidation. Bound coelenterazine adopts a Y-shaped conformation, enabling the deprotonated imidazopyrazinone component to attack O2 via a radical charge-transfer mechanism. A high emission intensity is secured by an aspartate from a conserved proton-relay system, which protonates the excited coelenteramide product. Another aspartate on the rim of the catalytic pocket fine-tunes the electronic state of coelenteramide and promotes the formation of the blue light-emitting phenolate anion. The results obtained also reveal structural features distinguishing flash-type from glow-type bioluminescence, providing insights that will guide the engineering of next-generation luciferase‒luciferin pairs for ultrasensitive optical bioassays.

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“…It has recently been suggested that an additional lesion of copper toxicosis may be an impairment in the blood clotting cascade (2). This suggestion was based on the observation that copper, either as a simple salt such as copper sulfate, or in the form of some complexes, such as copper aspirinate, copper penicillamine, or copper tyrosine, can inhibit the in vitro synthesis of prothrombin in a rat liver microsomal fraction (2-4).…”

mentioning

confidence: 99%

“…The inhibitory action of the copper complexes is believed to be the result of their ability to act as superoxide scavengers. The superoxide ion and/or peroxide and resultant reactants are thought to be directly involved in the vitamin K-dependent carboxylation step as they are involved in the production of the carboxylating species, perhaps through formation of the peroxybicarbonate anion or the peroxybicarbamate anion (2). In this To whom correspondence should be addressed.…”

mentioning

confidence: 99%

The Influence of High Concentrations of Dietary Copper on Vitamin K-Dependent Coagulation Factors

Keen¹,

Feldman²,

Knight³

et al. 1982

Experimental Biology and Medicine

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It has been shown that high concentrations of some copper complexes can inhibit in vitro the vitamin K-dependent carboxylation of specific glutamic residues. The present study was conducted in order to determine whether high levels of dietary copper would affect the circulating levels of blood clotting factors. Rats fed for 7 weeks purified diets containing 10 (control), 100, 1000, or 2000 pg/g Cu had liver copper concentrations of 4,4, 67, and 603 pglg Cu, respectively. The severity of the toxicity of the 2000 pg/g Cu diet was evidenced by four deaths in this diet group. Despite the severity of the copper toxicity, values for one-stage prothrombin, activated partial thromboplastin, and Russell's Viper Venom times were similar for all groups. In addition, dietary copper level had no effect on the circulating levels of the specific vitamin K-dependent coagulation factors 11, VII, IX, and X. These data provide evidence that an impairment in the blood clotting cascade is not a characteristic of dietary copper toxicosis.The experiment was terminated after 7 47 1 0037-9727/82/08047 1-05$01 . W O

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The Carboxylation of Preprothrombin

Cited by 4 publications

References 14 publications

Catalytic mechanism for Renilla-type luciferases

Catalytic mechanism for Renilla-type luciferases

A catalytic mechanism for Renilla-type bioluminescence

The Influence of High Concentrations of Dietary Copper on Vitamin K-Dependent Coagulation Factors

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