Crystal structure of the archaeosine synthase QueF-like-Insights into amidino transfer and tRNA recognition by the tunnel fold.
Proteins
; 85(1): 103-116, 2017 01.
Article
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| MEDLINE
| ID: mdl-27802572
ABSTRACT
The tunneling-fold (T-fold) structural superfamily has emerged as a versatile protein scaffold of diverse catalytic activities. This is especially evident in the pathways to the 7-deazaguanosine modified nucleosides of tRNA queuosine and archaeosine. Four members of the T-fold superfamily have been confirmed in these pathways and here we report the crystal structure of a fifth enzyme; the recently discovered amidinotransferase QueF-Like (QueF-L), responsible for the final step in the biosynthesis of archaeosine in the D-loop of tRNA in a subset of Crenarchaeota. QueF-L catalyzes the conversion of the nitrile group of the 7-cyano-7-deazaguanine (preQ0 ) base of preQ0 -modified tRNA to a formamidino group. The structure, determined in the presence of preQ0 , reveals a symmetric T-fold homodecamer of two head-to-head facing pentameric subunits, with 10 active sites at the inter-monomer interfaces. Bound preQ0 forms a stable covalent thioimide bond with a conserved active site cysteine similar to the intermediate previously observed in the nitrile reductase QueF. Despite distinct catalytic functions, phylogenetic distributions, and only 19% sequence identity, the two enzymes share a common preQ0 binding pocket, and likely a common mechanism of thioimide formation. However, due to tight twisting of its decamer, QueF-L lacks the NADPH binding site present in QueF. A large positively charged molecular surface and a docking model suggest simultaneous binding of multiple tRNA molecules and structure-specific recognition of the D-loop by a surface groove. The structure sheds light on the mechanism of nitrile amidation, and the evolution of diverse chemistries in a common fold. Proteins 2016; 85103-116. © 2016 Wiley Periodicals, Inc.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirimidinonas
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Pirroles
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Procesamiento Postranscripcional del ARN
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Proteínas Arqueales
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Pyrobaculum
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Amidinotransferasas
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Guanosina
Idioma:
En
Revista:
Proteins
Asunto de la revista:
BIOQUIMICA
Año:
2017
Tipo del documento:
Article