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Title: Structural basis of Qng1-mediated salvage of the micronutrient queuine from queuosine-5′-monophosphate as the biological substrate

Journal Article · · Nucleic Acids Research

Abstract Eukaryotic life benefits from—and ofttimes critically relies upon—the de novo biosynthesis and supply of vitamins and micronutrients from bacteria. The micronutrient queuosine (Q), derived from diet and/or the gut microbiome, is used as a source of the nucleobase queuine, which once incorporated into the anticodon of tRNA contributes to translational efficiency and accuracy. Here, we report high-resolution, substrate-bound crystal structures of the Sphaerobacter thermophilus queuine salvage protein Qng1 (formerly DUF2419) and of its human ortholog QNG1 (C9orf64), which together with biochemical and genetic evidence demonstrate its function as the hydrolase releasing queuine from queuosine-5′-monophosphate as the biological substrate. We also show that QNG1 is highly expressed in the liver, with implications for Q salvage and recycling. The essential role of this family of hydrolases in supplying queuine in eukaryotes places it at the nexus of numerous (patho)physiological processes associated with queuine deficiency, including altered metabolism, proliferation, differentiation and cancer progression.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Sponsoring Organization:
National Institutes of Health (NIH); Science Foundation Ireland; USDOE
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1908287
Journal Information:
Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 2 Vol. 51; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United Kingdom
Language:
English

References (74)

Mechanism and Substrate Specificity of tRNA-Guanine Transglycosylases (TGTs): tRNA-Modifying Enzymes from the Three Different Kingdoms of Life Share a Common Catalytic Mechanism journal October 2005
Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia journal January 2005
Solution structure of the nucleotide hydrolase BlsM: Implication of its substrate specificity journal July 2020
Effects of a Diet Deficient in Tyrosine and Queuine on Germfree Mice journal January 1997
Queuosine Modification of tRNA: A Case for Convergent Evolution journal September 2001
Queuine is incorporated into brain transfer RNA journal November 1989
A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition journal April 2016
Salvage of the nucleic acid base queuine from queuine-containing tRNA by animal cells journal November 1982
Activity of a transfer RNA modifying enzyme during the development of Drosophila and its relationship to the su(s) locus journal March 1973
Variations in tRNA modifications, particularly of their queuine content in higher eukaryotes. Its relation to malignancy grading journal January 1995
Queuine salvage in mammalian cells. Evidence that queuine is generated from queuosine 5'-phosphate. journal January 1984
Structure of an amniotic fluid component, 7-(4,5-cis-dihydroxy-1-cyclopenten-3-ylaminomethyl)-7-deazaguanine (queuine), a substrate for tRNA: guanine transglycosylase. journal September 1980
Purification and characterization of a Saccharomyces cerevisiae exoribonuclease which yields 5'-mononucleotides by a 5' leads to 3' mode of hydrolysis. journal April 1980
Preparation of selenomethionyl proteins for phase determination book January 1997
Recent advances in the structural mechanisms of DNA glycosylases journal January 2013
Queuosine salvage in fission yeast by Qng1-mediated hydrolysis to queuine journal October 2022
Structural Characterization of the Mammalian Deoxynucleotide N-Hydrolase Rcl and Its Stabilizing Interactions with Two Inhibitors journal December 2009
Structural Insights into the Mechanism of Base Excision by MBD4 journal July 2021
Structural and functional characterization of two unusual endonuclease III enzymes from Deinococcus radiodurans journal August 2015
(p)ppGpp Regulates a Bacterial Nucleosidase by an Allosteric Two-Domain Switch journal June 2019
Catalysis by nucleoside hydrolases journal December 2003
A DNA Glycosylase from Pyrobaculum aerophilum with an 8-Oxoguanine Binding Mode and a Noncanonical Helix-Hairpin-Helix Structure journal January 2005
Separation-of-Function Mutants Unravel the Dual-Reaction Mode of Human 8-Oxoguanine DNA Glycosylase journal January 2011
Microbes and Monoamines: Potential Neuropsychiatric Consequences of Dysbiosis journal March 2019
Kinetic Isotope Effect Studies of the Reaction Catalyzed by Uracil DNA Glycosylase:  Evidence for an Oxocarbenium Ion−Uracil Anion Intermediate journal November 2000
Evidence that the nucleic acid base queuine is incorporated intact into tRNA by animal cells journal March 1984
Structure of the modified nucleoside Q isolated from Escherichia coli transfer ribonucleic acid. 7-(4,5-cis-Dihydroxy-1-cyclopenten-3-ylaminomethyl)-7-deazaguanosine journal September 1975
Diversity of Archaeosine Synthesis in Crenarchaeota journal November 2011
Plant, Animal, and Fungal Micronutrient Queuosine Is Salvaged by Members of the DUF2419 Protein Family journal June 2014
The structure of Q* nucleoside isolated from rabbit liver transfer ribonucleic acid journal August 1976
Total synthesis of optically pure nucleoside Q. Determination of absolute configuration of natural nucleoside Q journal June 1979
Transition-State Analysis of the DNA Repair Enzyme MutY journal April 2008
Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA journal February 2000
Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe journal May 2010
Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells journal April 2011
Complete chemical structures of human mitochondrial tRNAs journal August 2020
Highly accurate protein structure prediction with AlphaFold journal July 2021
Structural basis for cytokinin production by LOG from Corynebacterium glutamicum journal August 2016
Prolonging healthy aging: Longevity vitamins and proteins journal October 2018
Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens journal September 2019
Queuosine Deficiency in Eukaryotes Compromises Tyrosine Production through Increased Tetrahydrobiopterin Oxidation journal April 2011
Deazaguanine derivatives, examples of crosstalk between RNA and DNA modification pathways journal December 2016
Structural and functional insights into human tRNA guanine transgylcosylase journal July 2021
Affinity electrophoresis for monitoring terminal phosphorylation and the presence of queuosine in RNA. Application of polyacrylamide containing a covalently bound boronic acid journal January 1985
C to U editing and modifications during the maturation of the mitochondrial tRNAASPin marsupials journal January 1995
Isolation of mammalian tRNAAspand tRNATyrby lectin-Sepharose affinity column chromatography journal January 1977
Enzymatic synthesis of Q*nucleoside containing mannose in the anticodon of tRNA: isolation of a novel mannosyltransferase from a cell-free extract of rat liver journal January 1977
The human tRNA-guanine transglycosylase displays promiscuous nucleobase preference but strict tRNA specificity journal May 2021
Preferential import of queuosine-modified tRNAs into Trypanosoma brucei mitochondrion is critical for organellar protein synthesis journal July 2021
Excision of thymine and 5-hydroxymethyluracil by the MBD4 DNA glycosylase domain: structural basis and implications for active DNA demethylation journal June 2012
Structure of theN-glycosidase MilB in complex with hydroxymethyl CMP reveals its Arg23 specifically recognizes the substrate and controls its entry journal June 2014
Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases journal December 2015
Queuine links translational control in eukaryotes to a micronutrient from bacteria journal February 2019
Degradation of several hypomodified mature tRNA species in Saccharomyces cerevisiae is mediated by Met22 and the 5′–3′ exonucleases Rat1 and Xrn1 journal April 2008
Phaser crystallographic software journal July 2007
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes journal July 2006
Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard journal December 2007
XDS journal January 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Features and development of Coot journal March 2010
Overview of the CCP 4 suite and current developments journal March 2011
REFMAC 5 for the refinement of macromolecular crystal structures journal March 2011
Towards automated crystallographic structure refinement with phenix.refine journal March 2012
SOLVE and RESOLVE: automated structure solution, density modification and model building journal November 2003
Recent developments in the PHENIX software for automated crystallographic structure determination journal November 2003
The nutrient factor queuine protects HeLa cells from hypoxic stress and improves metabolic adaptation to oxygen availability journal May 1994
Nuclear Functions Charge Ahead journal December 1998
Novel salvage of queuine from queuosine and absence of queuine synthesis in Chlorella pyrenoidosa and Chlamydomonas reinhardtii. journal December 1988
A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus journal December 2014
Queuine, a bacterial-derived hypermodified nucleobase, shows protection in in vitro models of neurodegeneration journal August 2021
Queuosine‐modified tRNAs confer nutritional control of protein translation journal August 2018
Queuine Salvaging in the Human Parasite Entamoeba histolytica journal August 2022
Queuine Micronutrient Deficiency Promotes Warburg Metabolism and Reversal of the Mitochondrial ATP Synthase in Hela Cells journal March 2020
The Queuine Micronutrient: Charting a Course from Microbe to Man journal April 2015

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