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Crystal structure of the archaeosine synthase QueF‐like—Insights into amidino transfer and tRNA recognition by the tunnel fold
Author(s) -
Mei Xianghan,
Alvarez Jonathan,
Bon Ramos Adriana,
Samanta Uttamkumar,
IwataReuyl Dirk,
Swairjo Manal A.
Publication year - 2017
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25202
Subject(s) - stereochemistry , active site , crenarchaeota , transfer rna , structural motif , docking (animal) , binding site , crystal structure , chemistry , protein structure , biology , enzyme , biochemistry , crystallography , rna , phylogenetic tree , gene , medicine , nursing
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 (preQ 0 ) base of preQ 0 ‐modified tRNA to a formamidino group. The structure, determined in the presence of preQ 0 , reveals a symmetric T‐fold homodecamer of two head‐to‐head facing pentameric subunits, with 10 active sites at the inter‐monomer interfaces. Bound preQ 0 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 preQ 0 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; 85:103–116. © 2016 Wiley Periodicals, Inc.