|Gene:||hisS||Accession Numbers: EG10453 (EcoCyc), b2514, ECK2510|
Subunit composition of
histidyl-tRNA synthetase = [HisS]2
histidyl-tRNA synthetase = HisS
Histidyl-tRNA synthetase (HisRS) is a member of the family of aminoacyl-tRNA synthetases, which interpret the genetic code by covalently linking amino acids to their specific tRNA molecules. The reaction is driven by ATP hydrolysis. HisRS belongs to the Class II aminoacyl tRNA synthetases, which share three regions of homology [Eriani90, Cusack91].
HisRS is a dimer in solution [Kalousek74]. The C-terminal domain of the protein is required for dimerization, while the N-terminal domain contains most of the catalytic activity. The two domains do not complement each other in trans [Augustine97]. Minimal active site fragments likely representing the ancestral "urzyme" have been studied [Li11].
Specificity determinants within tRNAHis that are important for recognition by HisRS have been identified; the unique G-1:C73 base pair was found to play a crucial role [Himeno89, Yan94, Fromant00, Rosen04, Guth07]. Specificity determinants and residues within HisRS that are important for catalytic activity have been investigated [Yan95, Ruhlmann97, Bovee99, Hawko01, Connolly04, Guth07], and a model for the catalytic cycle was proposed [Guth07]. The C-terminal domain of HisRS was found to be largely responsible for recognition of the tRNAHis anticodon [Yan96].
Crystal structures of HisRS have been determined, and a reaction mechanism was proposed [Arnez95, Arnez97]. Various types of experiments support a substrate-assisted concerted reaction mechanism [Guth05]. Catalysis may occur at sites alternating between the two monomers; conformational changes may be rate-limiting for product formation [Guth07, Guth09]. The mechanisms of substrate discrimination [Banik09, Banik10] and the aminoacylation reaction [Banik11] have been modeled.
Gene Citations: [Freedman85]
|Map Position: [2,637,323 <- 2,638,597] (56.84 centisomes)||Length: 1275 bp / 424 aa|
Molecular Weight of Polypeptide: 47.029 kD (from nucleotide sequence), 42 kD (experimental) [Kalousek74 ]
Molecular Weight of Multimer: 86 kD (experimental) [Kalousek74]
Unification Links: ASAP:ABE-0008278 , CGSC:624 , DIP:DIP-35894N , EchoBASE:EB0448 , EcoGene:EG10453 , EcoliWiki:b2514 , Mint:MINT-1236095 , ModBase:P60906 , OU-Microarray:b2514 , PortEco:hisS , PR:PRO_000022903 , Pride:P60906 , Protein Model Portal:P60906 , RefSeq:NP_417009 , RegulonDB:EG10453 , SMR:P60906 , String:511145.b2514 , UniProt:P60906
Relationship Links: InterPro:IN-FAMILY:IPR002314 , InterPro:IN-FAMILY:IPR004154 , InterPro:IN-FAMILY:IPR004516 , InterPro:IN-FAMILY:IPR006195 , InterPro:IN-FAMILY:IPR015807 , Panther:IN-FAMILY:PTHR11476 , PDB:Structure:1HTT , PDB:Structure:1KMM , PDB:Structure:1KMN , PDB:Structure:2EL9 , Pfam:IN-FAMILY:PF00587 , Pfam:IN-FAMILY:PF03129 , Prosite:IN-FAMILY:PS50862
|Biological Process:||GO:0006427 - histidyl-tRNA aminoacylation
GO:0006412 - translation [UniProtGOA11a]
GO:0006418 - tRNA aminoacylation for protein translation [GOA01a]
|Molecular Function:||GO:0004821 - histidine-tRNA ligase activity
[GOA01, GOA01a, Kalousek74]
GO:0042803 - protein homodimerization activity [Kalousek74]
GO:0000166 - nucleotide binding [UniProtGOA11a, GOA01a]
GO:0004812 - aminoacyl-tRNA ligase activity [UniProtGOA11a, GOA01a]
GO:0005524 - ATP binding [UniProtGOA11a, GOA01a]
GO:0016874 - ligase activity [UniProtGOA11a]
|Cellular Component:||GO:0005829 - cytosol
[DiazMejia09, Ishihama08, LopezCampistrou05]
GO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a, GOA01a]
|MultiFun Terms:||information transfer → protein related → amino acid -activation|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB Lennox||No||37||Aerobic||7||No [Baba06, Comment 1]|
Enzymatic reaction of: histidyl-tRNA synthetase
EC Number: 18.104.22.168
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.
The reaction is physiologically favored in the direction shown.
In Pathways: tRNA charging
|Chain||2 -> 424|
10/20/97 Gene b2514 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10453; confirmed by SwissProt match.
Arnez95: Arnez JG, Harris DC, Mitschler A, Rees B, Francklyn CS, Moras D (1995). "Crystal structure of histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate." EMBO J 14(17);4143-55. PMID: 7556055
Arnez97: Arnez JG, Augustine JG, Moras D, Francklyn CS (1997). "The first step of aminoacylation at the atomic level in histidyl-tRNA synthetase." Proc Natl Acad Sci U S A 94(14);7144-9. PMID: 9207058
Augustine97: Augustine J, Francklyn C (1997). "Design of an active fragment of a class II aminoacyl-tRNA synthetase and its significance for synthetase evolution." Biochemistry 36(12);3473-82. PMID: 9131996
Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554
Banik09: Banik SD, Nandi N (2009). "Orientation and distance dependent chiral discrimination in the first step of the aminoacylation reaction: integrated molecular orbital and semi-empirical method (ONIOM) based calculation." Colloids Surf B Biointerfaces 74(2);468-76. PMID: 19682871
Connolly04: Connolly SA, Rosen AE, Musier-Forsyth K, Francklyn CS (2004). "G-1:C73 recognition by an arginine cluster in the active site of Escherichia coli histidyl-tRNA synthetase." Biochemistry 43(4);962-9. PMID: 14744140
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Eriani90: Eriani G, Delarue M, Poch O, Gangloff J, Moras D (1990). "Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs." Nature 347(6289);203-6. PMID: 2203971
Freedman85: Freedman R, Gibson B, Donovan D, Biemann K, Eisenbeis S, Parker J, Schimmel P (1985). "Primary structure of histidine-tRNA synthetase and characterization of hisS transcripts." J Biol Chem 1985;260(18);10063-8. PMID: 2991272
Guth05: Guth E, Connolly SH, Bovee M, Francklyn CS (2005). "A substrate-assisted concerted mechanism for aminoacylation by a class II aminoacyl-tRNA synthetase." Biochemistry 44(10);3785-94. PMID: 15751955
Hawko01: Hawko SA, Francklyn CS (2001). "Covariation of a specificity-determining structural motif in an aminoacyl-tRNA synthetase and a tRNA identity element." Biochemistry 40(7);1930-6. PMID: 11329259
Himeno89: Himeno H, Hasegawa T, Ueda T, Watanabe K, Miura K, Shimizu M (1989). "Role of the extra G-C pair at the end of the acceptor stem of tRNA(His) in aminoacylation." Nucleic Acids Res 17(19);7855-63. PMID: 2678006
Li11: Li L, Weinreb V, Francklyn C, Carter CW (2011). "Histidyl-tRNA synthetase urzymes: Class I and II aminoacyl tRNA synthetase urzymes have comparable catalytic activities for cognate amino acid activation." J Biol Chem 286(12);10387-95. PMID: 21270472
LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532
Rosen06: Rosen AE, Brooks BS, Guth E, Francklyn CS, Musier-Forsyth K (2006). "Evolutionary conservation of a functionally important backbone phosphate group critical for aminoacylation of histidine tRNAs." RNA 12(7);1315-22. PMID: 16741232
Yan95: Yan W, Francklyn C (1995). "tRNA selection by a class II aminoacyl-tRNA synthetase: the role of accessory domains and inter-domain communication in RNA recognition." Nucleic Acids Symp Ser (33);167-9. PMID: 8643360
Yan96: Yan W, Augustine J, Francklyn C (1996). "A tRNA identity switch mediated by the binding interaction between a tRNA anticodon and the accessory domain of a class II aminoacyl-tRNA synthetase." Biochemistry 35(21);6559-68. PMID: 8639604
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