Vertebrate 5-Hydroxyisourate Hydrolase Identification, Function, Structure, and Evolutionary Relationship with Transthyretin

Zanotti, Giuseppe; Ramazzina, Ileana; Cendron, Laura; Folli, Claudia; Percudani, Riccardo; Berni, Rodolfo

doi:10.1007/978-3-642-00646-3_6

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…Given the same intron/ exon structures of the genes encoding HIUase and TTR, the first coding exon encodes a signal peptide in TTR and a type 2 PTS in HIUase. 12 Notably, conservation of the intron position and sequence similarity in the first exon suggest that, after gene duplication, the PTS sequence of HIUase was transformed into the TTR signal peptide by point mutations. 12 These observations, along with the fact that TTR itself is mainly produced by the liver from which it is secreted into the circulation, prompt us to postulate that the TTR ancestor evolved into the plasma carrier TTR through amino acid replacements affecting the first exon of the encoding gene to give rise to a signal peptide, while maintaining the same expression localization.…”

Section: Discussionmentioning

confidence: 99%

Probing the Evolution of Hydroxyisourate Hydrolase into Transthyretin through Active-Site Redesign

Cendron

Ramazzina

Percudani

et al. 2011

Journal of Molecular Biology

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Section: Discussionmentioning

confidence: 99%

Probing the Evolution of Hydroxyisourate Hydrolase into Transthyretin through Active-Site Redesign

Cendron

Ramazzina

Percudani

et al. 2011

Journal of Molecular Biology

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Sequential Molecular Events of Functional Trade-Offs in 5-Hydroxyisourate Hydrolase Before and After Gene Duplication Led to the Evolution of Transthyretin During Chordate Diversification

Yamauchi

Kasai

2018

J Mol Evol

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Transthyretin (TTR), a plasma thyroid hormone distributor protein (THDP), emerged from 5-hydroxyisourate hydrolase (HIUHase), an enzyme involved in urate metabolism, by gene duplication at a stage of chordate evolution. Comparison of amino acid sequences revealed the presence of two His-rich segments in the primitive TTRs. Using several HIUHase and TTR mutants, we investigated 5-hydroxyisourate (HIU) hydrolysis activity and thyroid hormone (TH) binding activity to elucidate how a novel function as a THDP arose. Lancelet HIUHase was found to have higher enzyme activity than trout HIUHase. Two amino acid substitutions, R54E/Y119T, at the active sites of HIUHase, exerted weak [I]-3,3',5-triiodo-L-thyronine ([I]T3) binding activity with a concomitant loss of HIU hydrolysis activity. Addition of 3×His (3×H) to the N-terminal end weakened HIU hydrolysis activity of both lancelet and trout HIUHases, whereas it enhanced T3-binding activity of HIUHase R54E/Y119T. Trout HIUHase 3×H R54E/Y119T had higher [I]T3-binding activity than that of lancelet HIUHase 3×H R54E/Y119T, with a K of 143 nM, and displayed metal dependency and no TH binding specificity. Deletion of the N-terminal His-rich segment from lamprey TTR decreased T3-binding activity, while addition of 3×H to trout TTR increased T3-binding activity, while maintaining TH binding specificity. Our results suggest that functional trade-offs of HIU hydrolysis activity with TH binding activity might have sequentially occurred before and after gene duplication, and that TH binding specificity and high-affinity sites may have been acquired later in the course of TTR evolution.

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Reenacting the Birth of a Function: Functional Divergence of HIUases and Transthyretins as Inferred by Evolutionary and Biophysical Studies

et al. 2021

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Vertebrate 5-Hydroxyisourate Hydrolase Identification, Function, Structure, and Evolutionary Relationship with Transthyretin

Cited by 3 publications

References 32 publications

Probing the Evolution of Hydroxyisourate Hydrolase into Transthyretin through Active-Site Redesign

Probing the Evolution of Hydroxyisourate Hydrolase into Transthyretin through Active-Site Redesign

Sequential Molecular Events of Functional Trade-Offs in 5-Hydroxyisourate Hydrolase Before and After Gene Duplication Led to the Evolution of Transthyretin During Chordate Diversification

Reenacting the Birth of a Function: Functional Divergence of HIUases and Transthyretins as Inferred by Evolutionary and Biophysical Studies

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