|Gene:||aroL||Accession Numbers: EG10082 (MetaCyc), b0388, ECK0383|
Species: Escherichia coli K-12 substr. MG1655
Shikimate kinase is involved in the fifth step of the chorismate pathway, which leads to the biosynthesis of aromatic amino acids. Shikimate kinase catalyzes the formation of shikimate 3-phosphate from shikimate and ATP. There are two shikimate kinase enzymes, I (AroK) and II (AroL). The isoenzymes are separable and presumably monofunctional [Millar86a].
The amino acid sequences of shikimate kinase I and II shows 30% homology over the entire length of both proteins [Whipp95]. Shikimate kinase I is encoded by aroK and shikimate kinase II is encoded by aroL. The expression of aroK unlike that of aroL, which is controlled by the TyrR and TrpR repressors, appears to be constitutive [Ely79, Lawley94]. Expression of aroL is regulated by the tyrR gene product protein with tyrosine or tryptophan as a co-repressor [Millar86a].
Shikimate kinase I has a much lower affinity (approximately 100-fold) for shikimate than shikimate kinase II. Shikimate II seems to be the dominant enzyme of the pathway with shikimate I playing a secondary role. The enzyme activity is dependent on the presence of a divalent cation as a cofactor. [DeFeyter86a]
Presumably the strains lacking the two major DAHP synthase isoenzymes (AroF and AroG) cannot accumulate an internal pool of shikimate that is sufficient for shikimate kinase I alone to carry out the phosphorylation, but the reaction can be performed by shikimate kinase II. Studies on the affinity of the shikimate kinase isoenzymes for shikimate support this interpretation. [DeFeyter86b]
The level of shikimate kinase can be repressed and derepressed. Both tyrosine and tryptophan, but not phenylalanine are apparently involved in this control. Starvation for both of these amino acids results in derepression. In a fully repressed cell, shikimate kinase I is the predominant shikimate kinase activity. However, a mutation in tyrR or the partial starvation of an aromatic auxotroph for tyrosine and tryptophan appears to alter only the level of shikimate kinase II which now becomes the cell's major shikimate kinase activity [Ely79]. In contrast to shikimate kinase II, the activity of shikimate kinase I in the cell is independent of both the amount of extracellular aromatic amino acids and the level of tyrR gene products [LobnerOlesen92a].
Amino acids and biosynthetic intermediates were tested for inhibitory effects. Neither the aromatic amino acids, either singly or all together, nor a mixture of aromatic amino acids and vitamins at the concentrations used caused inhibition of either shikimate kinase I or shikimate kinase II activity. Similarly neither chorismic acid nor prephenic acid, two key biosynthetic intermediates in the aromatic pathway, had a significant effect on these shikimate kinase activities. [DeFeyter86a]
|Map Position: [405,629 -> 406,153]|
Molecular Weight of Polypeptide: 19.151 kD (from nucleotide sequence), 21.4 kD (experimental) [DeFeyter86a ]
Unification Links: ASAP:ABE-0001353 , CGSC:999 , EchoBASE:EB0080 , EcoGene:EG10082 , EcoliWiki:b0388 , ModBase:P0A6E1 , OU-Microarray:b0388 , PortEco:aroL , PR:PRO_000022151 , Pride:P0A6E1 , Protein Model Portal:P0A6E1 , RefSeq:NP_414922 , RegulonDB:EG10082 , SMR:P0A6E1 , String:511145.b0388 , Swiss-Model:P0A6E1 , UniProt:P0A6E1
Relationship Links: InterPro:IN-FAMILY:IPR000623 , InterPro:IN-FAMILY:IPR023000 , InterPro:IN-FAMILY:IPR027417 , InterPro:IN-FAMILY:IPR027544 , Pfam:IN-FAMILY:PF01202 , Prints:IN-FAMILY:PR01100 , Prosite:IN-FAMILY:PS01128
|Biological Process:||GO:0009073 - aromatic amino acid family biosynthetic process
[UniProtGOA11a, GOA06, GOA01a, Oldiges04]
GO:0008652 - cellular amino acid biosynthetic process [UniProtGOA11a]
GO:0009423 - chorismate biosynthetic process [UniProtGOA12]
GO:0016310 - phosphorylation [UniProtGOA11a]
GO:0019632 - shikimate metabolic process [Gaudet10]
|Molecular Function:||GO:0000287 - magnesium ion binding
GO:0004765 - shikimate kinase activity [GOA06, GOA01, GOA01a, DeFeyter86a]
GO:0046872 - metal ion binding [UniProtGOA11a, DeFeyter86a]
GO:0000166 - nucleotide binding [UniProtGOA11a]
GO:0005524 - ATP binding [UniProtGOA11a, GOA06]
GO:0016301 - kinase activity [UniProtGOA11a]
GO:0016740 - transferase activity [UniProtGOA11a]
|Cellular Component:||GO:0005737 - cytoplasm
[UniProtGOA11, UniProtGOA11a, GOA06]
GO:0005829 - cytosol [DiazMejia09]
|MultiFun Terms:||metabolism → biosynthesis of building blocks → amino acids → chorismate|
Enzymatic reaction of: shikimate kinase
EC Number: 126.96.36.199
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
This reaction is reversible.
In Pathways: superpathway of chorismate metabolism , superpathway of aromatic amino acid biosynthesis , superpathway of L-phenylalanine biosynthesis , superpathway of L-tyrosine biosynthesis , superpathway of L-tryptophan biosynthesis , chorismate biosynthesis I , chorismate biosynthesis from 3-dehydroquinate
Cofactor Binding Comment: The enzyme activity was dependent on the presence of a divalent cation as a cofactor. Mg2+ was the most effective cation, but significant activity was obtained with all of the other divalent cations tested (Mn2+, Co2+, Fe2+, Ca2+, K+)
|Chain||2 -> 174|
|Nucleotide-Phosphate-Binding-Region||12 -> 17|
|Protein-Segment||112 -> 126|
10/20/97 Gene b0388 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10082; confirmed by SwissProt match.
DeFeyter86: DeFeyter RC, Davidson BE, Pittard J (1986). "Nucleotide sequence of the transcription unit containing the aroL and aroM genes from Escherichia coli K-12." J Bacteriol 1986;165(1);233-9. PMID: 3001025
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
Millar86a: Millar G, Lewendon A, Hunter MG, Coggins JR (1986). "The cloning and expression of the aroL gene from Escherichia coli K12. Purification and complete amino acid sequence of shikimate kinase II, the aroL-gene product." Biochem J 1986;237(2);427-37. PMID: 3026317
Oldiges04: Oldiges M, Kunze M, Degenring D, Sprenger GA, Takors R (2004). "Stimulation, monitoring, and analysis of pathway dynamics by metabolic profiling in the aromatic amino acid pathway." Biotechnol Prog 20(6);1623-33. PMID: 15575692
Pereira07: Pereira JH, Vasconcelos IB, Oliveira JS, Caceres RA, de Azevedo WF, Basso LA, Santos DS (2007). "Shikimate kinase: a potential target for development of novel antitubercular agents." Curr Drug Targets 8(3);459-68. PMID: 17348838
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