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Chemical Structure| 65996-58-9 Chemical Structure| 65996-58-9

Structure of 9-Deazaguanine
CAS No.: 65996-58-9

Chemical Structure| 65996-58-9

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9-Deazaguanine is a nucleoside analog that effectively inhibits purine nucleoside phosphorylase (PNP), with potential application value in anticancer and immunosuppressive therapies.

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Katharina Sievers ;

Abstract: The eukaryotic tRNA guanine transglycosylase (TGT) is an RNA modifying enzyme incorporating queuinea hypermodified guanine derivative, into the tRN AsAsp,Asn.His,Ty,. While both subunits of the functionaheterodimer have been crystalized individually, much of our understanding of its dimer interface orrecognition of a target RNA has been inferred from its more thoroughly studied bacterial homologHowever, since bacterial TGT, by incorporating queuine precursor preQ,, deviates not only in functionbut as a homodimer, also in its subunit architecture, any inferences regarding the subunit association ofthe eukaryotic heterodimer or the significance of its unique catalytically inactive subunit are based onunstable footing. Here, we report the crystal structure of human TGT in its heterodimeric form and incomplex with a 25-mer stem loop RNA, enabling detailed analysis of its dimer interface and interactionwith a minimal substrate RNA. Based on a model of bound tRNA, we addressed a potential functionalrole of the catalytically inactive subunit QTRT2 by UV-crosslinking and mutagenesis experimentsidentifying the two-stranded BEBF-sheet of the OTRT2 subunit as an additional RNA-binding motif.

Keywords: Queuine ; tRNA modifcation ; RN A-binding protein ; transglycosylase ; heterodimer ; eukaryotic ; structural biology ; X-raycrystallography

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Sievers, Katharina ; Welp, Luisa ; Urlaub, Henning ; Ficner, Ralf ;

Abstract: The eukaryotic tRNA guanine transglycosylase (TGT) is an RNA modifying enzyme incorporating queuine, a hypermodified guanine derivative, into the tRNAsAsp,Asn,His,Tyr. While both subunits of the functional heterodimer have been crystallized individually, much of our understanding of its dimer interface or recognition of a target RNA has been inferred from its more thoroughly studied bacterial homolog. However, since bacterial TGT, by incorporating queuine precursor preQ1, deviates not only in function, but as a homodimer, also in its subunit architecture, any inferences regarding the subunit association of the eukaryotic heterodimer or the significance of its unique catalytically inactive subunit are based on unstable footing. Here, we report the crystal structure of human TGT in its heterodimeric form and in complex with a 25-mer stem loop RNA, enabling detailed anal. of its dimer interface and interaction with a minimal substrate RNA. Based on a model of bound tRNA, we addressed a potential functional role of the catalytically inactive subunit QTRT2 by UV-crosslinking and mutagenesis experiments, identifying the two-stranded βEβF-sheet of the QTRT2 subunit as an addnl. RNA-binding motif.

Keywords: Queuine ; RNA-binding protein ; X-ray crystallography ; eukaryotic ; heterodimer ; structural biology ; tRNA modification ; transglycosylase

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Product Details of 9-Deazaguanine

CAS No. :65996-58-9
Formula : C6H6N4O
M.W : 150.14
SMILES Code : O=C1C(NC=C2)=C2N=C(N)N1
MDL No. :MFCD09540493
InChI Key :FFYPRJYSJODFFD-UHFFFAOYSA-N
Pubchem ID :135461003

Safety of 9-Deazaguanine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

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Preparing Stock Solutions 1mg 5mg 10mg

1 mM

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6.66mL

1.33mL

0.67mL

33.30mL

6.66mL

3.33mL

66.60mL

13.32mL

6.66mL

 

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