EzCatDB: S00230
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00230
RLCP classification3.944.220700.2 : Transfer
CATH domainDomain 13.20.20.105 : TIM BarrelCatalytic domain
E.C.2.4.2.29
CSA1pud


Enzyme Name
UniProtKBKEGG

P28720Q9X1P7
Protein nameQueuine tRNA-ribosyltransferaseQueuine tRNA-ribosyltransferasetRNA-guanine transglycosylase
guanine insertion enzyme
tRNA transglycosylase
Q-insertase
queuine transfer ribonucleate ribosyltransferase
transfer ribonucleate glycosyltransferase
tRNA guanine transglycosidase
guanine, queuine-tRNA transglycosylase
queuine tRNA-ribosyltransferase
TGT
[tRNA]-guanine:queuine tRNA-D-ribosyltransferase
transfer ribonucleic acid guanine transglycosylase
SynonymsEC 2.4.2.29
tRNA-guanine transglycosylase
Guanine insertion enzyme
EC 2.4.2.29
tRNA-guanine transglycosylase
Guanine insertion enzyme
RefSeqYP_162098.2 (Protein)
NC_006526.2 (DNA/RNA sequence)
NP_229361.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
PfamPF01702 (TGT)
[Graphical view]
PF01702 (TGT)
[Graphical view]


UniProtKB:Accession NumberP28720Q9X1P7
Entry nameTGT_ZYMMOTGT_THEMA
Activity[tRNA]-guanine + queuine = [tRNA]-queuine + guanine.,[tRNA]-guanine + 7-aminomethyl-7-carbaguanine = [tRNA]-7-aminomethyl-7-carbaguanine + guanine.[tRNA]-guanine + queuine = [tRNA]-queuine + guanine.,[tRNA]-guanine + 7-aminomethyl-7-carbaguanine = [tRNA]-7-aminomethyl-7-carbaguanine + guanine.
SubunitMonomer.
Subcellular location

CofactorBinds 1 zinc ion per subunit.Binds 1 zinc ion per subunit (By similarity).

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00038C01977C01449C01978C00242
CompoundZinctRNA guanineQueuinetRNA queuineGuanineenzyme-tRNA covalent intermediate
Typeheavy metalamide group,amine group,nucleic acidsamide group,amine group,aromatic ring (with nitrogen atoms),carbohydrateamide group,amine group,carbohydrate,nucleic acidsamide group,amine group,aromatic ring (with nitrogen atoms)
ChEBI29105

17433

16235

PubChem32051

114881

764

              
1efzABound:_ZNUnboundAnalogue:PRFUnboundUnboundUnbound
1enuABound:_ZNUnboundUnboundUnboundAnalogue:APZUnbound
1f3eABound:_ZNUnboundUnboundUnboundAnalogue:DPZUnbound
1k4gABound:_ZNUnboundAnalogue:AIQUnboundUnboundUnbound
1k4hABound:_ZNUnboundAnalogue:APQUnboundUnboundUnbound
1n2vABound:_ZNUnboundAnalogue:BDIUnboundUnboundUnbound
1ozmABound:_ZNUnboundUnboundUnboundUnboundUnbound
1ozqABound:_ZNUnboundAnalogue:PRFUnboundUnboundUnbound
1p0bABound:_ZNUnboundAnalogue:PQ0UnboundUnboundUnbound
1p0dABound:_ZNUnboundUnboundUnboundUnboundUnbound
1p0eABound:_ZNUnboundAnalogue:PRFUnboundUnboundUnbound
1pudABound:_ZNUnboundUnboundUnboundUnboundUnbound
1pxgABound:_ZNUnboundAnalogue:PRFUnboundUnboundUnbound
1q2rABound:_ZNUnboundUnboundUnboundAnalogue:9DGBound:ASP 280-ROB(chain E)
1q2rBBound:_ZNUnboundUnboundUnboundAnalogue:9DGUnbound
1q2rCBound:_ZNUnboundUnboundUnboundAnalogue:9DGBound:ASP 280-ROB(chain F)
1q2rDBound:_ZNUnboundUnboundUnboundAnalogue:9DGUnbound
1q2sABound:_ZNUnboundUnboundAnalogue:A-G-C-A-C-G-G-C-U-PQ1-U-A-A-A-C-C-G-U-G-C(chain E)UnboundUnbound
1q2sBBound:_ZNUnboundUnboundUnboundUnboundUnbound
1q2sCBound:_ZNUnboundUnboundUnboundAnalogue:9DGAnalogue:ASP 280-ROB(chain F)
1q2sDBound:_ZNUnboundUnboundUnboundUnboundUnbound
1q4wABound:_ZNUnboundUnboundUnboundAnalogue:DQUUnbound
1q63ABound:_ZNUnboundAnalogue:AIQUnboundUnboundUnbound
1q65ABound:_ZNUnboundAnalogue:BHBUnboundUnboundUnbound
1q66ABound:_ZNUnboundAnalogue:KMBUnboundUnboundUnbound
1r5yABound:_ZNUnboundUnboundUnboundAnalogue:DQUUnbound
1s38ABound:_ZNUnboundUnboundUnboundAnalogue:MAQUnbound
1s39ABound:_ZNUnboundUnboundUnboundAnalogue:AQOUnbound
1wkdABound:_ZNUnboundUnboundUnboundUnboundUnbound
1wkeABound:_ZNUnboundUnboundUnboundUnboundUnbound
1wkfABound:_ZNUnboundUnboundUnboundUnboundUnbound
1y5vABound:_ZNUnboundAnalogue:NE8UnboundUnboundUnbound
1y5wABound:_ZNUnboundAnalogue:NEZUnboundUnboundUnbound
1y5xABound:_ZNUnboundAnalogue:E89UnboundUnboundUnbound
1y5xDBound:_ZNUnboundAnalogue:E89UnboundUnboundUnbound
2ashABound:_ZNUnboundUnboundUnboundUnboundUnbound
2ashBBound:_ZNUnboundUnboundUnboundUnboundUnbound
2ashCBound:_ZNUnboundUnboundUnboundUnboundUnbound
2ashDBound:_ZNUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P28720 & literature [29], [31]
pdbCatalytic residuesCofactor-binding residuescomment
           
1efzAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
mutant S103A
1enuAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1f3eAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1k4gAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1k4hAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1n2vAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1ozmAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
mutant Y106F
1ozqAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
mutant Y106F
1p0bAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1p0dAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1p0eAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1pudAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1pxgAASP  102;        
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
mutant D280E
1q2rAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q2rBASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q2rCASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q2rDASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q2sAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q2sBASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q2sCASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q2sDASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q4wAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q63AASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q65AASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1q66AASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1r5yAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1s38AASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1s39AASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1wkdA        ;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
mutant D102A
1wkeAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
mutant D156A
1wkfAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
mutant D156Y
1y5vAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1y5wAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1y5xAASP  102;ASP  280
CYS  318;CYS  320;CYS  323;HIS  349(Zinc binding)
 
1y5xDASP 1102;ASP 1280
CYS 1318;CYS 1320;CYS 1323;HIS 1349(Zinc binding)
 
2ashAASP   89;ASP  261
CYS  299;CYS  301;CYS  304;HIS  330(Zinc binding)
 
2ashBASP   89;ASP  261
CYS  299;CYS  301;CYS  304;HIS  330(Zinc binding)
 
2ashCASP   89;ASP  261
CYS  299;CYS  301;CYS  304;HIS  330(Zinc binding)
 
2ashDASP   89;ASP  261
CYS  299;CYS  301;CYS  304;HIS  330(Zinc binding)
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[15]Fig.4, p.15738
[16]p.2853-2855
[21]Fig.4, p.145
[22]Fig.2, p.14128-14132
[27]Fig.1, p.1072-1074
[29]Fig.2, Fig.4, Fig.7, p.42376
[31]Fig.1, p.772
[32]p.786-787
[33]Fig.2, p.56

references
[1]
PubMed ID6696916
JournalBiochim Biophys Acta
Year1984
Volume781
Pages64-75
AuthorsFarkas WR, Jacobson KB, Katze JR
TitleSubstrate and inhibitor specificity of tRNA-guanine ribosyltransferase
[2]
PubMed ID3117541
JournalEur J Biochem
Year1987
Volume168
Pages219-25
AuthorsHaumont E, Droogmans L, Grosjean H
TitleEnzymatic formation of queuosine and of glycosyl queuosine in yeast tRNAs microinjected into Xenopus laevis oocytes. The effect of the anticodon loop sequence
[3]
PubMed ID8494901
JournalBiochemistry
Year1993
Volume32
Pages5239-46
AuthorsCurnow AW, Kung FL, Koch KA, Garcia GA
TitletRNA-guanine transglycosylase from Escherichia coli
[4]
PubMed ID8323579
JournalJ Mol Biol
Year1993
Volume231
Pages489-97
AuthorsGarcia GA, Koch KA, Chong S
TitletRNA-guanine transglycosylase from Escherichia coli. Overexpression, purification and quaternary structure
[5]
PubMed ID8003468
JournalBiochemistry
Year1994
Volume33
Pages7041-6
AuthorsReuter K, Chong S, Ullrich F, Kersten H, Garcia GA
TitleSerine 90 is required for enzymic activity by tRNA-guanine transglycosylase from Escherichia coli
[6]
PubMed ID7748954
JournalBiochimie
Year1994
Volume76
Pages1183-91
AuthorsCurnow AW, Garcia GA
TitletRNA-guanine transglycosylase from Escherichia coli
[7]
PubMed ID7528209
JournalJ Biol Chem
Year1994
Volume269
Pages32221-5
AuthorsNakanishi S, Ueda T, Hori H, Yamazaki N, Okada N, Watanabe K
TitleA UGU sequence in the anticodon loop is a minimum requirement for recognition by Escherichia coli tRNA-guanine transglycosylase
[8]
PubMed ID7893665
JournalBiochemistry
Year1995
Volume34
Pages3694-701
AuthorsChong S, Curnow AW, Huston TJ, Garcia GA
TitletRNA-guanine transglycosylase from Escherichia coli is a zinc metalloprotein. Site-directed mutagenesis studies to identify the zinc ligands
[9]
PubMed ID7492556
JournalBiochemistry
Year1995
Volume34
Pages15539-44
AuthorsHoops GC, Townsend LB, Garcia GA
TitleMechanism-based inactivation of tRNA-guanine transglycosylase from Escherichia coli by 2-amino-5-(fluoromethyl)pyrrolo[2,3-d]pyrimidin-4 (3H)-one
[10]
PubMed ID7578154
JournalBiochemistry
Year1995
Volume34
Pages15381-7
AuthorsHoops GC, Townsend LB, Garcia GA
TitletRNA-guanine transglycosylase from Escherichia coli
[11]
PubMed ID7665516
JournalJ Bacteriol
Year1995
Volume177
Pages5284-8
AuthorsReuter K, Ficner R
TitleSequence analysis and overexpression of the Zymomonas mobilis tgt gene encoding tRNA-guanine transglycosylase
[12]
PubMed ID7615526
JournalJ Biol Chem
Year1995
Volume270
Pages17264-7
AuthorsCurnow AW, Garcia GA
TitletRNA-guanine transglycosylase from Escherichia coli. Minimal tRNA structure and sequence requirements for recognition.
[13]
PubMed ID8579355
JournalArch Biochem Biophys
Year1996
Volume326
Pages1-7
AuthorsDeshpande KL, Seubert PH, Tillman DM, Farkas WR, Katze JR
TitleCloning and characterization of cDNA encoding the rabbit tRNA-guanine transglycosylase 60-kilodalton subunit
[14]
PubMed ID8608154
JournalBiochemistry
Year1996
Volume35
Pages3133-9
AuthorsGarcia GA, Tierney DL, Chong S, Clark K, Penner-Hahn JE
TitleX-ray absorption spectroscopy of the zinc site in tRNA-guanine transglycosylase from Escherichia coli
[15]
CommentsX-ray crystallography
PubMed ID8961936
JournalBiochemistry
Year1996
Volume35
Pages15734-9
AuthorsRomier C, Reuter K, Suck D, Ficner R
TitleMutagenesis and crystallographic studies of Zymomonas mobilis tRNA-guanine transglycosylase reveal aspartate 102 as the active site nucleophile
Related PDB1wkd,1wke,1wkf
[16]
CommentsX-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
Medline ID96256303
PubMed ID8654383
JournalEMBO J
Year1996
Volume15
Pages2850-7
AuthorsRomier C, Reuter K, Suck D, Ficner R
TitleCrystal structure of tRNA-guanine transglycosylase
Related PDB1pud
Related UniProtKBP28720
[17]
PubMed ID8860000
JournalProteins
Year1996
Volume24
Pages516-9
AuthorsRomier C, Ficner R, Reuter K, Suck D
TitlePurification, crystallization, and preliminary x-ray diffraction studies of tRNA-guanine transglycosylase from Zymomonas mobilis
[18]
PubMed ID9369241
JournalFEBS Lett
Year1997
Volume416
Pages93-8
AuthorsRomier C, Meyer JE, Suck D
TitleSlight sequence variations of a common fold explain the substrate specificities of tRNA-guanine transglycosylases from the three kingdoms
[19]
PubMed ID9055203
JournalJ Protein Chem
Year1997
Volume16
Pages11-7
AuthorsGarcia GA, Chong S
TitleCysteine 265 is in the active site of, but is not essential for catalysis by tRNA-guanine transglycosylase (TGT) from Escherichia coli
[20]
PubMed ID9403840
JournalMed Microbiol Immunol (Berl)
Year1997
Volume186
Pages125-34
AuthorsBereswill S, Fassbinder F, Volzing C, Haas R, Reuter K, Ficner R, Kist M
TitleCloning and functional characterization of the genes encoding 3-dehydroquinate synthase (aroB) and tRNA-guanine transglycosylase (tgt) from Helicobacter pylori
[21]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 10-381, AND MUTAGENESIS OF SER-102.
PubMed ID10413112
JournalFEBS Lett
Year1999
Volume454
Pages142-6
AuthorsGradler U, Ficner R, Garcia GA, Stubbs MT, Klebe G, Reuter K
TitleMutagenesis and crystallographic studies of Zymomonas mobilis tRNA-guanine transglycosylase to elucidate the role of serine 103 for enzymatic activity
Related PDB1efz
Related UniProtKBP28720
[22]
PubMed ID11714265
JournalBiochemistry
Year2001
Volume40
Pages14123-33
AuthorsKittendorf JD, Barcomb LM, Nonekowski ST, Garcia GA
TitletRNA-guanine transglycosylase from Escherichia coli
[23]
PubMed ID11255023
JournalGene
Year2001
Volume265
Pages205-12
AuthorsDeshpande KL, Katze JR
TitleCharacterization of cDNA encoding the human tRNA-guanine transglycosylase (TGT) catalytic subunit
[24]
CommentsX-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
Medline ID21103718
PubMed ID11178905
JournalJ Mol Biol
Year2001
Volume306
Pages455-67
AuthorsGradler U, Gerber HD, Goodenough-Lashua DM, Garcia GA, Ficner R, Reuter K, Stubbs MT, Klebe G
TitleA new target for shigellosis
Related PDB1f3e
Related UniProtKBP28720
[25]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 11-385.
PubMed ID11921407
JournalChembiochem
Year2002
Volume3
Pages250-3
AuthorsMeyer EA, Brenk R, Castellano RK, Furler M, Klebe G, Diederich F
TitleDe novo design, synthesis, and in vitro evaluation of inhibitors for prokaryotic tRNA-guanine transglycosylase
Related PDB1k4g,1k4h
Related UniProtKBP28720
[26]
PubMed ID11751936
JournalJ Biol Chem
Year2002
Volume277
Pages7178-82
AuthorsNonekowski ST, Kung FL, Garcia GA
TitleThe Escherichia coli tRNA-guanine transglycosylase can recognize and modify DNA
[27]
CommentsX-ray crystallography
PubMed ID14523925
JournalChembiochem
Year2003
Volume4
Pages1066-77
AuthorsBrenk R, Stubbs MT, Heine A, Reuter K, Klebe G
TitleFlexible adaptations in the structure of the tRNA-modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug design.
Related PDB1ozm,1ozq,1p0b,1p0d,1p0e
[28]
PubMed ID12581659
JournalCurr Opin Struct Biol
Year2003
Volume13
Pages49-55
AuthorsFerre-D'Amare AR
TitleRNA-modifying enzymes.
[29]
PubMed ID12909636
JournalJ Biol Chem
Year2003
Volume278
Pages42369-76
AuthorsKittendorf JD, Sgraja T, Reuter K, Klebe G, Garcia GA
TitleAn essential role for aspartate 264 in catalysis by tRNA-guanine transglycosylase from Escherichia coli.
Related PDB1pxg
[30]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 11-385.
PubMed ID12646024
JournalJ Med Chem
Year2003
Volume46
Pages1133-43
AuthorsBrenk R, Naerum L, Gradler U, Gerber HD, Garcia GA, Reuter K, Stubbs MT, Klebe G
TitleVirtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis.
Related PDB1n2v
Related UniProtKBP28720
[31]
PubMed ID14513020
JournalNat Struct Biol
Year2003
Volume10
Pages772-3
AuthorsCorrell CC
TitleCaught in the act of modifying tRNA.
[32]
PubMed ID12949492
JournalNat Struct Biol
Year2003
Volume10
Pages781-8
AuthorsXie W, Liu X, Huang RH
TitleChemical trapping and crystal structure of a catalytic tRNA guanine transglycosylase covalent intermediate.
Related PDB1q2r,1q2s
[33]
PubMed ID15050823
JournalJ Mol Biol
Year2004
Volume338
Pages55-75
AuthorsBrenk R, Meyer EA, Reuter K, Stubbs MT, Garcia GA, Diederich F, Klebe G
TitleCrystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening.
Related PDB1q4w,1q63,1q65,1q66,1r5y
[34]
JournalHelv Chim Acta
Year2004
Volume87
Pages1333-56g
AuthorsMeyer EA, Furler M, Diederich F, Brenk R, Klebe G
TitleSynthesis and in vitro evaluation of 2-aminoquinazolin-4(3h)-one-based inhibitors for tRNA-guanine transglycosylase (tgt).
Related PDB1s38,1s39

comments
Although this enzyme binds a zinc ion, it is not involved in catalysis.
According to the literature [31] and [32], the catalytic reaction proceeds as follows:
(1) Asp280 makes a nucleophilic attack on the C1' atom of tRNA ribose, while Asp102 acts as a general acid to protonate the leaving group, N9 atom of guanine. This reaction proceeds via SN2-like mechanism, forming an enzyme-tRNA covalent intermediate.
(2) Asp102 acts as a general base activate the N9 atom of queine(or preQ1), the acceptor group, by deprotonating it.
(3) The activated queine (or preQ1) makes a nucleophilic attack on the C1' atom of the intermediate, completing the reaction.

createdupdated
2005-03-292009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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