M00177
type: Enzyme
cath: Rossmann fold
cath: Isoleucyl-tRNA Synthetase; domain 2
cath: Isoleucyl-tRNA Synthetase; Domain 1
cath: http://ezcatdb.cbrc.jp/EzCatDB/cath/2.-.-.-
ec: https://purl.uniprot.org/enzyme/6.1.1.5
macie: M0309
uniprot: P41972
uniprot: P56690
kegg enzyme: isoleucine---tRNA ligase
kegg enzyme: isoleucyl-tRNA synthetase
kegg pathway: Valine, leucine and isoleucine biosynthesis
kegg pathway: Aminoacyl-tRNA biosynthesis
kegg cofactor: Zinc
kegg substrate: ATP
kegg substrate: L-Isoleucine
kegg substrate: tRNA(Ile)
kegg product: AMP
kegg product: Pyrophosphate
kegg product: L-Isoleucyl-tRNA(Ile)
pdb: 1ffyA01
pdb: 1qu2A01
pdb: 1qu3A01
pdb: 1ileA03
pdb: 1jzqA03
pdb: 1jzsA03
pdb: 1ffyA02
pdb: 1qu2A02
pdb: 1qu3A02
pdb: 1ileA02
pdb: 1jzqA02
pdb: 1jzsA02
pdb: 1udzA
pdb: 1udzB
pdb: 1ue0A
pdb: 1ue0B
pdb: 1ffyA03
pdb: 1qu2A03
pdb: 1qu3A03
pdb: 1ileA01
pdb: 1jzqA01
pdb: 1jzsA01
pdb: 1ffyA04
pdb: 1qu2A04
pdb: 1qu3A04
active site residues resources: Rational design of femtomolar inhibitors of isoleucyl tRNA synthetase from a binding model for pseudomonic acid-A.
active site residues resources: 1jzq
references: Zinc-dependent tRNA binding by a peptide element within a tRNA synthetase.
references: Valyl-tRNA, isoleucyl-tRNA and tyrosyl-tRNA synthetase from baker's yeast. Substrate specificity with regard to ATP analogs and mechanism of the aminoacylation reaction.
references: A stereochemical and positional isotope exchange study of the mechanism of activation of isoleucine by isoleucyl-tRNA synthetase from Escherichia coli.
references: NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase.
references: Evidence from cassette mutagenesis for a structure-function motif in a protein of unknown structure.
references: Nonprotein amino acid furanomycin, unlike isoleucine in chemical structure, is charged to isoleucine tRNA by isoleucyl-tRNA synthetase and incorporated into protein.
references: Understanding structural relationships in proteins of unsolved three-dimensional structure.
references: Nuclear overhauser effect studies of the conformations of Mg(alpha, beta-methylene)ATP bound to E. coli isoleucyl-tRNA synthetase.
references: Isoleucyl-tRNA synthetase from the ciliated protozoan Tetrahymena thermophila. DNA sequence, gene regulation, and leucine zipper motifs.
references: A 15N-1H nuclear magnetic resonance study on the interaction between isoleucine tRNA and isoleucyl-tRNA synthetase from Escherichia coli.
references: Thiol ligation of two zinc atoms to a class I tRNA synthetase: evidence for unshared thiols and role in amino acid binding and utilization.
references: Probing the metal binding sites of Escherichia coli isoleucyl-tRNA synthetase.
references: Residues in a class I tRNA synthetase which determine selectivity of amino acid recognition in the context of tRNA.
references: C-terminal zinc-containing peptide required for RNA recognition by a class I tRNA synthetase.
references: Mutational analysis suggests the same design for editing activities of two tRNA synthetases.
references: Aminoacylation error correction.
references: Proofreading in trans by an aminoacyl-tRNA synthetase: a model for single site editing by isoleucyl-tRNA synthetase.
references: Characterization of isoleucyl-tRNA synthetase from Staphylococcus aureus. I: Kinetic mechanism of the substrate activation reaction studied by transient and steady-state techniques.
references: Sieves in sequence.
references: Enzyme structure with two catalytic sites for double-sieve selection of substrate.
references: Autonomous folding of a C-terminal inhibitory fragment of Escherichia coli isoleucine-tRNA synthetase.
references: Insights into editing from an ile-tRNA synthetase structure with tRNAile and mupirocin.
references: Rational design of femtomolar inhibitors of isoleucyl tRNA synthetase from a binding model for pseudomonic acid-A.
references: Errors from selective disruption of the editing center in a tRNA synthetase.
references: The fidelity of the translation of the genetic code.
references: Editing by a tRNA synthetase: DNA aptamer-induced translocation and hydrolysis of a misactivated amino acid.
references: Active site of an aminoacyl-tRNA synthetase dissected by energy-transfer-dependent fluorescence.
references: Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase.
references: Mutational separation of two pathways for editing by a class I tRNA synthetase.
references: Blocking site-to-site translocation of a misactivated amino acid by mutation of a class I tRNA synthetase.
references: Interstice mutations that block site-to-site translocation of a misactivated amino acid bound to a class I tRNA synthetase.
references: Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA synthetase and its complex with L-valine.
comment: Although this enzyme binds zinc ions, the binding sites are not conserved, away from active sites, suggesting that zinc ions are not involved in catalysis. The detailed catalytic mechanism has not been elucidated yet. However, this enzyme catalyzes two successive transfer reactions. (A) Transfer of the adenylate from ATP (the first substrate) to the carboxylate of the second substrate, isoleucine: This reaction results in the formation of leucinyl-adenylate (intermediate) and the release of the inorganic pyrophosphate. (B) Transfer of the acyl group from the intermediate to the 3'-end of tRNA(Ile).

Rossmann fold
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.50.620
catalytic domain: index.html

Isoleucyl-tRNA Synthetase; domain 2
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.90.740.10

Isoleucyl-tRNA Synthetase; Domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/1.10.730.10

Valine, leucine and isoleucine biosynthesis
type: KeggPathway
references: KEGG:MAP00290

Aminoacyl-tRNA biosynthesis
type: KeggPathway
references: KEGG:MAP00970

Zinc
type: KeggCofactor
references: KEGG:C00038
compound type: heavy metal
references: CHEBI:29105
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ATP
type: KeggSubstrate
references: KEGG:C00002
compound type: amine group
compound type: nucleotide
references: CHEBI:15422
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

L-Isoleucine
type: KeggSubstrate
references: KEGG:C00407
compound type: amino acids
references: CHEBI:17191
references: CHEBI:58045
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

tRNA(Ile)
type: KeggSubstrate
references: KEGG:C01644
compound type: nucleic acids

AMP
type: KeggProduct
references: KEGG:C00020
compound type: amine group
compound type: nucleotide
references: CHEBI:16027
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Pyrophosphate
type: KeggProduct
references: KEGG:C00013
compound type: phosphate group/phosphate ion
references: CHEBI:29888
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

L-Isoleucyl-tRNA(Ile)
type: KeggProduct
references: KEGG:C03127
compound type: amino acids
compound type: nucleic acids

1ffyA01
type: Pdb
references: 1ffy
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ffy
catalytic residue: HIS 67;LYS 595
main chain in catalysis: GLY 593

1qu2A01
type: Pdb
references: 1qu2
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1qu2
catalytic residue: HIS 67;LYS 595
main chain in catalysis: GLY 593

1qu3A01
type: Pdb
references: 1qu3
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1qu3
catalytic residue: HIS 67;LYS 595
main chain in catalysis: GLY 593

1ileA03
type: Pdb
references: 1ile
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ile
catalytic residue: HIS 57;LYS 591
main chain in catalysis: GLY 589

1jzqA03
type: Pdb
references: 1jzq
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1jzq
catalytic residue: HIS 57;LYS 591
main chain in catalysis: GLY 589

1jzsA03
type: Pdb
references: 1jzs
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1jzs
catalytic residue: HIS 57;LYS 591
main chain in catalysis: GLY 589

Zinc-dependent tRNA binding by a peptide element within a tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9184155
journal: Biochemistry
volume: 36
pages: 6739-44
published year: 1997
authors:
  item: Glasfeld E
  item: Schimmel P

Valyl-tRNA, isoleucyl-tRNA and tyrosyl-tRNA synthetase from baker's yeast. Substrate specificity with regard to ATP analogs and mechanism of the aminoacylation reaction.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/782885
journal: Eur J Biochem
volume: 66
pages: 493-7
published year: 1976
authors:
  item: Freist W
  item: von der Haar F
  item: Faulhammer H
  item: Cramer F

A stereochemical and positional isotope exchange study of the mechanism of activation of isoleucine by isoleucyl-tRNA synthetase from Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/6340735
journal: Biochemistry
volume: 22
pages: 1229-36
published year: 1983
authors:
  item: Lowe G
  item: Sproat BS
  item: Tansley G
  item: Cullis PM

NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/3322383
journal: Biochemistry
volume: 26
pages: 6531-8
published year: 1987
authors:
  item: Kohda D
  item: Kawai G
  item: Yokoyama S
  item: Kawakami M
  item: Mizushima S
  item: Miyazawa T

Evidence from cassette mutagenesis for a structure-function motif in a protein of unknown structure.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/3282306
journal: Science
volume: 240
pages: 521-3
published year: 1988
authors:
  item: Clarke ND
  item: Lien DC
  item: Schimmel P

Nonprotein amino acid furanomycin, unlike isoleucine in chemical structure, is charged to isoleucine tRNA by isoleucyl-tRNA synthetase and incorporated into protein.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2182633
journal: J Biol Chem
volume: 265
pages: 6931-5
published year: 1990
authors:
  item: Kohno T
  item: Kohda D
  item: Haruki M
  item: Yokoyama S
  item: Miyazawa T

Understanding structural relationships in proteins of unsolved three-dimensional structure.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2183216
journal: Proteins
volume: 7
pages: 99-111
published year: 1990
authors:
  item: Burbaum JJ
  item: Starzyk RM
  item: Schimmel P

Nuclear overhauser effect studies of the conformations of Mg(alpha, beta-methylene)ATP bound to E. coli isoleucyl-tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2025282
journal: Biochem Biophys Res Commun
volume: 176
pages: 682-9
published year: 1991
authors:
  item: Williams JS
  item: Rosevear PR

Isoleucyl-tRNA synthetase from the ciliated protozoan Tetrahymena thermophila. DNA sequence, gene regulation, and leucine zipper motifs.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1371507
journal: J Biol Chem
volume: 267
pages: 4592-9
published year: 1992
authors:
  item: Csank C
  item: Martindale DW

A 15N-1H nuclear magnetic resonance study on the interaction between isoleucine tRNA and isoleucyl-tRNA synthetase from Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8199246
journal: Biochimie
volume: 75
pages: 1109-15
published year: 1993
authors:
  item: Niimi T
  item: Kawai G
  item: Takayanagi M
  item: Noguchi T
  item: Hayashi N
  item: Kohno T
  item: Muto Y
  item: Watanabe K
  item: Miyazawa T
  item: Yokoyama S

Thiol ligation of two zinc atoms to a class I tRNA synthetase: evidence for unshared thiols and role in amino acid binding and utilization.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7947832
journal: Biochemistry
volume: 33
pages: 14213-20
published year: 1994
authors:
  item: Landro JA
  item: Schmidt E
  item: Schimmel P
  item: Tierney DL
  item: Penner-Hahn JE

Probing the metal binding sites of Escherichia coli isoleucyl-tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8286369
journal: Biochemistry
volume: 33
pages: 398-402
published year: 1994
authors:
  item: Xu B
  item: Trawick B
  item: Krudy GA
  item: Phillips RM
  item: Zhou L
  item: Rosevear PR

Residues in a class I tRNA synthetase which determine selectivity of amino acid recognition in the context of tRNA.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7669778
journal: Biochemistry
volume: 34
pages: 11204-10
published year: 1995
authors:
  item: Schmidt E
  item: Schimmel P

C-terminal zinc-containing peptide required for RNA recognition by a class I tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8672449
journal: Biochemistry
volume: 35
pages: 4139-45
published year: 1996
authors:
  item: Glasfeld E
  item: Landro JA
  item: Schimmel P

Mutational analysis suggests the same design for editing activities of two tRNA synthetases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8611551
journal: Biochemistry
volume: 35
pages: 5596-601
published year: 1996
authors:
  item: Lin L
  item: Schimmel P

Aminoacylation error correction.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8900273
journal: Nature
volume: 384
pages: 33-4
published year: 1996
authors:
  item: Lin L
  item: Hale SP
  item: Schimmel P

Proofreading in trans by an aminoacyl-tRNA synthetase: a model for single site editing by isoleucyl-tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8692688
journal: Nucleic Acids Res
volume: 24
pages: 2505-10
published year: 1996
authors:
  item: Jakubowski H

Characterization of isoleucyl-tRNA synthetase from Staphylococcus aureus. I: Kinetic mechanism of the substrate activation reaction studied by transient and steady-state techniques.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9822629
journal: J Biol Chem
volume: 273
pages: 31680-90
published year: 1998
authors:
  item: Pope AJ
  item: Lapointe J
  item: Mensah L
  item: Benson N
  item: Brown MJ
  item: Moore KJ

Sieves in sequence.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9575099
journal: Science
volume: 280
pages: 541
published year: 1998
authors:
  item: Fersht AR

Enzyme structure with two catalytic sites for double-sieve selection of substrate.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9554847
journal: Science
volume: 280
pages: 578-82
published year: 1998
authors:
  item: Nureki O
  item: Vassylyev DG
  item: Tateno M
  item: Shimada A
  item: Nakama T
  item: Fukai S
  item: Konno M
  item: Hendrickson TL
  item: Schimmel P
  item: Yokoyama S
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Autonomous folding of a C-terminal inhibitory fragment of Escherichia coli isoleucine-tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10446363
journal: Biochim Biophys Acta
volume: 1433
pages: 103-9
published year: 1999
authors:
  item: Michaels JE
  item: Shiba K
  item: Miller WT

Insights into editing from an ile-tRNA synthetase structure with tRNAile and mupirocin.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
medline id: 99377249
references: http://www.ncbi.nlm.nih.gov/pubmed/10446055
journal: Science
volume: 285
pages: 1074-7
published year: 1999
authors:
  item: Silvian LF
  item: Wang J
  item: Steitz TA
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P41972

Rational design of femtomolar inhibitors of isoleucyl tRNA synthetase from a binding model for pseudomonic acid-A.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10821672
journal: Biochemistry
volume: 39
pages: 6003-11
published year: 2000
authors:
  item: Brown MJ
  item: Mensah LM
  item: Doyle ML
  item: Broom NJ
  item: Osbourne N
  item: Forrest AK
  item: Richardson CM
  item: O'Hanlon PJ
  item: Pope AJ

Errors from selective disruption of the editing center in a tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10889024
journal: Biochemistry
volume: 39
pages: 8180-6
published year: 2000
authors:
  item: Hendrickson TL
  item: Nomanbhoy TK
  item: Schimmel P

The fidelity of the translation of the genetic code.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11732604
journal: Acta Biochim Pol
volume: 48
pages: 323-35
published year: 2001
authors:
  item: Sankaranarayanan R
  item: Moras D

Editing by a tRNA synthetase: DNA aptamer-induced translocation and hydrolysis of a misactivated amino acid.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11284704
journal: Biochemistry
volume: 40
pages: 4478-83
published year: 2001
authors:
  item: Farrow MA
  item: Schimmel P

Active site of an aminoacyl-tRNA synthetase dissected by energy-transfer-dependent fluorescence.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11412966
journal: Bioorg Med Chem Lett
volume: 11
pages: 1485-91
published year: 2001
authors:
  item: Nomanbhoy TK
  item: Schimmel P

Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11584022
journal: J Biol Chem
volume: 276
pages: 47387-93
published year: 2001
authors:
  item: Nakama T
  item: Nureki O
  item: Yokoyama S
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Mutational separation of two pathways for editing by a class I tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11864608
journal: Mol Cell
volume: 9
pages: 353-62
published year: 2002
authors:
  item: Hendrickson TL
  item: Nomanbhoy TK
  item: de Crecy-Lagard V
  item: Fukai S
  item: Nureki O
  item: Yokoyama S
  item: Schimmel P

Blocking site-to-site translocation of a misactivated amino acid by mutation of a class I tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11782529
journal: Proc Natl Acad Sci U S A
volume: 99
pages: 585-90
published year: 2002
authors:
  item: Bishop AC
  item: Nomanbhoy TK
  item: Schimmel P

Interstice mutations that block site-to-site translocation of a misactivated amino acid bound to a class I tRNA synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12515858
journal: Proc Natl Acad Sci U S A
volume: 100
pages: 490-4
published year: 2003
authors:
  item: Bishop AC
  item: Beebe K
  item: Schimmel PR

Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA synthetase and its complex with L-valine.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/14672940
journal: J Biol Chem
volume: 279
pages: 8396-402
published year: 2004
authors:
  item: Fukunaga R
  item: Fukai S
  item: Ishitani R
  item: Nureki O
  item: Yokoyama S
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

isoleucyl-transfer ribonucleate synthetase
type: KeggEnzyme

isoleucyl-transfer RNA synthetase
type: KeggEnzyme

isoleucine-transfer RNA ligase
type: KeggEnzyme

isoleucine-tRNA synthetase
type: KeggEnzyme

isoleucine translase
type: KeggEnzyme

Analogue
compound: tRNA(Ile)
pdb: 1ffyA01
ligand het code: C-C-C-A-C (chain T:3'-terminus)

Analogue
compound: tRNA(Ile)
pdb: 1qu2A01
ligand het code: C-C-C-A-C (chain T:3'-terminus)

Analogue
compound: tRNA(Ile)
pdb: 1qu3A01
ligand het code: C-C-C-A-C (chain T:3'-terminus)

Analogue
pdb: 1jzqA03
ligand het code: ILA

ReferenceForCatalyticMechanism
reference index: 22

ReferenceForCatalyticMechanism
reference index: 28