DB code: M00177

CATH domain 3.40.50.620 : Rossmann fold Catalytic domain
3.90.740.10 : Isoleucyl-tRNA Synthetase; domain 2
1.10.730.10 : Isoleucyl-tRNA Synthetase; Domain 1
2.-.-.- :
E.C. 6.1.1.5
CSA
M-CSA
MACiE M0309

CATH domain Related DB codes (homologues)
1.10.730.10 : Isoleucyl-tRNA Synthetase; Domain 1 T00106
3.40.50.620 : Rossmann fold S00314 S00549 S00316 S00317 S00318 S00315 T00085 T00249 D00300 M00178 T00106 T00114

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P41972 Isoleucyl-tRNA synthetase
EC 6.1.1.5
Isoleucine--tRNA ligase
IleRS
PF08264 (Anticodon_1)
PF00133 (tRNA-synt_1)
PF06827 (zf-FPG_IleRS)
[Graphical View]
P56690 Isoleucyl-tRNA synthetase
EC 6.1.1.5
Isoleucine--tRNA ligase
IleRS
PF08264 (Anticodon_1)
PF00133 (tRNA-synt_1)
[Graphical View] 		YP_144333.1 (Protein)
NC_006461.1 (DNA/RNA sequence)

KEGG enzyme name
isoleucine---tRNA ligase
isoleucyl-tRNA synthetase
isoleucyl-transfer ribonucleate synthetase
isoleucyl-transfer RNA synthetase
isoleucine-transfer RNA ligase
isoleucine-tRNA synthetase
isoleucine translase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P41972 SYI1_STAAU ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-isoleucyl-tRNA(Ile). Monomer. Cytoplasm. Binds 1 zinc ion per subunit.
P56690 SYI_THET8 ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-isoleucyl-tRNA(Ile). Monomer. Cytoplasm. Binds 2 zinc ions per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00290 Valine, leucine and isoleucine biosynthesis
MAP00970 Aminoacyl-tRNA biosynthesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00002 C00407 C01644 C00020 C00013 C03127
E.C.
Compound Zinc ATP L-Isoleucine tRNA(Ile) AMP Pyrophosphate L-Isoleucyl-tRNA(Ile) Isoleucinyl-adenylate
Type heavy metal amine group,nucleotide amino acids nucleic acids amine group,nucleotide phosphate group/phosphate ion amino acids,nucleic acids
ChEBI 29105
 29105
 		15422
 15422
 		17191
 58045
 17191
 58045
 		16027
 16027
 		29888
 29888
PubChem 32051
 32051
 		5957
 5957
 		6306
 7043901
 6306
 7043901
 		6083
 6083
 		1023
 21961011
 1023
 21961011
1ffyA01 Unbound Unbound Unbound Analogue:C-C-C-A-C (chain T:3'-terminus) Unbound Unbound Unbound Unbound
1qu2A01 Unbound Unbound Unbound Analogue:C-C-C-A-C (chain T:3'-terminus) Unbound Unbound Unbound Unbound
1qu3A01 Unbound Unbound Unbound Analogue:C-C-C-A-C (chain T:3'-terminus) Unbound Unbound Unbound Unbound
1ileA03 Bound:2x_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1jzqA03 Bound:2x_ZN Unbound Unbound Unbound Unbound Unbound Unbound Analogue:ILA
1jzsA03 Bound:2x_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ffyA02 Bound:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qu2A02 Bound:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qu3A02 Bound:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ileA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1jzqA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1jzsA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1udzA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1udzB Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ue0A Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ue0B Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ffyA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qu2A03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qu3A03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ileA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1jzqA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1jzsA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ffyA04 Bound:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qu2A04 Bound:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qu3A04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1jzq & literature [22]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ffyA01 HIS 67;LYS 595 GLY 593
1qu2A01 HIS 67;LYS 595 GLY 593
1qu3A01 HIS 67;LYS 595 GLY 593
1ileA03 HIS 57;LYS 591 GLY 589
1jzqA03 HIS 57;LYS 591 GLY 589
1jzsA03 HIS 57;LYS 591 GLY 589
1ffyA02
1qu2A02
1qu3A02
1ileA02
1jzqA02
1jzsA02
1udzA
1udzB
1ue0A
1ue0B
1ffyA03
1qu2A03
1qu3A03
1ileA01
1jzqA01
1jzsA01
1ffyA04
1qu2A04
1qu3A04

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[22]
[28]

References
[1]
Resource
Comments
Medline ID
PubMed ID 782885
Journal Eur J Biochem
Year 1976
Volume 66
Pages 493-7
Authors Freist W, von der Haar F, Faulhammer H, Cramer F
Title 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.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 6340735
Journal Biochemistry
Year 1983
Volume 22
Pages 1229-36
Authors Lowe G, Sproat BS, Tansley G, Cullis PM
Title A stereochemical and positional isotope exchange study of the mechanism of activation of isoleucine by isoleucyl-tRNA synthetase from Escherichia coli.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3322383
Journal Biochemistry
Year 1987
Volume 26
Pages 6531-8
Authors Kohda D, Kawai G, Yokoyama S, Kawakami M, Mizushima S, Miyazawa T
Title NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3282306
Journal Science
Year 1988
Volume 240
Pages 521-3
Authors Clarke ND, Lien DC, Schimmel P
Title Evidence from cassette mutagenesis for a structure-function motif in a protein of unknown structure.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2182633
Journal J Biol Chem
Year 1990
Volume 265
Pages 6931-5
Authors Kohno T, Kohda D, Haruki M, Yokoyama S, Miyazawa T
Title Nonprotein amino acid furanomycin, unlike isoleucine in chemical structure, is charged to isoleucine tRNA by isoleucyl-tRNA synthetase and incorporated into protein.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 2183216
Journal Proteins
Year 1990
Volume 7
Pages 99-111
Authors Burbaum JJ, Starzyk RM, Schimmel P
Title Understanding structural relationships in proteins of unsolved three-dimensional structure.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 2025282
Journal Biochem Biophys Res Commun
Year 1991
Volume 176
Pages 682-9
Authors Williams JS, Rosevear PR
Title Nuclear overhauser effect studies of the conformations of Mg(alpha, beta-methylene)ATP bound to E. coli isoleucyl-tRNA synthetase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 1371507
Journal J Biol Chem
Year 1992
Volume 267
Pages 4592-9
Authors Csank C, Martindale DW
Title Isoleucyl-tRNA synthetase from the ciliated protozoan Tetrahymena thermophila. DNA sequence, gene regulation, and leucine zipper motifs.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8199246
Journal Biochimie
Year 1993
Volume 75
Pages 1109-15
Authors Niimi T, Kawai G, Takayanagi M, Noguchi T, Hayashi N, Kohno T, Muto Y, Watanabe K, Miyazawa T, Yokoyama S
Title A 15N-1H nuclear magnetic resonance study on the interaction between isoleucine tRNA and isoleucyl-tRNA synthetase from Escherichia coli.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 7947832
Journal Biochemistry
Year 1994
Volume 33
Pages 14213-20
Authors Landro JA, Schmidt E, Schimmel P, Tierney DL, Penner-Hahn JE
Title Thiol ligation of two zinc atoms to a class I tRNA synthetase: evidence for unshared thiols and role in amino acid binding and utilization.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8286369
Journal Biochemistry
Year 1994
Volume 33
Pages 398-402
Authors Xu B, Trawick B, Krudy GA, Phillips RM, Zhou L, Rosevear PR
Title Probing the metal binding sites of Escherichia coli isoleucyl-tRNA synthetase.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 7669778
Journal Biochemistry
Year 1995
Volume 34
Pages 11204-10
Authors Schmidt E, Schimmel P
Title Residues in a class I tRNA synthetase which determine selectivity of amino acid recognition in the context of tRNA.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8672449
Journal Biochemistry
Year 1996
Volume 35
Pages 4139-45
Authors Glasfeld E, Landro JA, Schimmel P
Title C-terminal zinc-containing peptide required for RNA recognition by a class I tRNA synthetase.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 8611551
Journal Biochemistry
Year 1996
Volume 35
Pages 5596-601
Authors Lin L, Schimmel P
Title Mutational analysis suggests the same design for editing activities of two tRNA synthetases.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8900273
Journal Nature
Year 1996
Volume 384
Pages 33-4
Authors Lin L, Hale SP, Schimmel P
Title Aminoacylation error correction.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8692688
Journal Nucleic Acids Res
Year 1996
Volume 24
Pages 2505-10
Authors Jakubowski H
Title Proofreading in trans by an aminoacyl-tRNA synthetase: a model for single site editing by isoleucyl-tRNA synthetase.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9184155
Journal Biochemistry
Year 1997
Volume 36
Pages 6739-44
Authors Glasfeld E, Schimmel P
Title Zinc-dependent tRNA binding by a peptide element within a tRNA synthetase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9822629
Journal J Biol Chem
Year 1998
Volume 273
Pages 31680-90
Authors Pope AJ, Lapointe J, Mensah L, Benson N, Brown MJ, Moore KJ
Title Characterization of isoleucyl-tRNA synthetase from Staphylococcus aureus. I: Kinetic mechanism of the substrate activation reaction studied by transient and steady-state techniques.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9575099
Journal Science
Year 1998
Volume 280
Pages 541
Authors Fersht AR
Title Sieves in sequence.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9554847
Journal Science
Year 1998
Volume 280
Pages 578-82
Authors Nureki O, Vassylyev DG, Tateno M, Shimada A, Nakama T, Fukai S, Konno M, Hendrickson TL, Schimmel P, Yokoyama S
Title Enzyme structure with two catalytic sites for double-sieve selection of substrate.
Related PDB 1ile
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10446363
Journal Biochim Biophys Acta
Year 1999
Volume 1433
Pages 103-9
Authors Michaels JE, Shiba K, Miller WT
Title Autonomous folding of a C-terminal inhibitory fragment of Escherichia coli isoleucine-tRNA synthetase.
Related PDB
Related UniProtKB
[22]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
Medline ID 99377249
PubMed ID 10446055
Journal Science
Year 1999
Volume 285
Pages 1074-7
Authors Silvian LF, Wang J, Steitz TA
Title Insights into editing from an ile-tRNA synthetase structure with tRNAile and mupirocin.
Related PDB 1ffy 1qu2 1qu3
Related UniProtKB P41972
[23]
Resource
Comments
Medline ID
PubMed ID 10821672
Journal Biochemistry
Year 2000
Volume 39
Pages 6003-11
Authors Brown MJ, Mensah LM, Doyle ML, Broom NJ, Osbourne N, Forrest AK, Richardson CM, O'Hanlon PJ, Pope AJ
Title Rational design of femtomolar inhibitors of isoleucyl tRNA synthetase from a binding model for pseudomonic acid-A.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 10889024
Journal Biochemistry
Year 2000
Volume 39
Pages 8180-6
Authors Hendrickson TL, Nomanbhoy TK, Schimmel P
Title Errors from selective disruption of the editing center in a tRNA synthetase.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11732604
Journal Acta Biochim Pol
Year 2001
Volume 48
Pages 323-35
Authors Sankaranarayanan R, Moras D
Title The fidelity of the translation of the genetic code.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 11284704
Journal Biochemistry
Year 2001
Volume 40
Pages 4478-83
Authors Farrow MA, Schimmel P
Title Editing by a tRNA synthetase: DNA aptamer-induced translocation and hydrolysis of a misactivated amino acid.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 11412966
Journal Bioorg Med Chem Lett
Year 2001
Volume 11
Pages 1485-91
Authors Nomanbhoy TK, Schimmel P
Title Active site of an aminoacyl-tRNA synthetase dissected by energy-transfer-dependent fluorescence.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11584022
Journal J Biol Chem
Year 2001
Volume 276
Pages 47387-93
Authors Nakama T, Nureki O, Yokoyama S
Title Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase.
Related PDB 1jzq 1jzs
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 11864608
Journal Mol Cell
Year 2002
Volume 9
Pages 353-62
Authors Hendrickson TL, Nomanbhoy TK, de Crecy-Lagard V, Fukai S, Nureki O, Yokoyama S, Schimmel P
Title Mutational separation of two pathways for editing by a class I tRNA synthetase.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 11782529
Journal Proc Natl Acad Sci U S A
Year 2002
Volume 99
Pages 585-90
Authors Bishop AC, Nomanbhoy TK, Schimmel P
Title Blocking site-to-site translocation of a misactivated amino acid by mutation of a class I tRNA synthetase.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 12515858
Journal Proc Natl Acad Sci U S A
Year 2003
Volume 100
Pages 490-4
Authors Bishop AC, Beebe K, Schimmel PR
Title Interstice mutations that block site-to-site translocation of a misactivated amino acid bound to a class I tRNA synthetase.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 14672940
Journal J Biol Chem
Year 2004
Volume 279
Pages 8396-402
Authors Fukunaga R, Fukai S, Ishitani R, Nureki O, Yokoyama S
Title Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA synthetase and its complex with L-valine.
Related PDB 1udz 1ue0
Related UniProtKB

Comments
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).

Created Updated
2004-09-14 2009-02-26