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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
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MetaCyc Enzyme: shikimate kinase II

Gene: aroL Accession Numbers: EG10082 (MetaCyc), b0388, ECK0383

Species: Escherichia coli K-12 substr. MG1655

Summary:
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 [Millar86].

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 [Millar86].

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. [DeFeyter86]

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. [DeFeyter86a]

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 [LobnerOlesen92].

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. [DeFeyter86]

Citations: [DeFeyter86b]

Locations: cytosol

Map Position: [405,629 -> 406,153]

Molecular Weight of Polypeptide: 19.151 kD (from nucleotide sequence), 21.4 kD (experimental) [DeFeyter86 ]

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

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0009073 - aromatic amino acid family biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a, Oldiges04]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
GO:0009423 - chorismate biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0016310 - phosphorylation Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0000287 - magnesium ion binding Inferred from experiment Inferred by computational analysis [GOA06, DeFeyter86]
GO:0004765 - shikimate kinase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, DeFeyter86]
GO:0046872 - metal ion binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, DeFeyter86]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a, GOA06]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids chorismate

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: shikimate kinase

EC Number: 2.7.1.71

shikimate + ATP <=> shikimate 3-phosphate + ADP + H+

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 phenylalanine, tyrosine, and tryptophan biosynthesis , superpathway of phenylalanine biosynthesis , superpathway of tyrosine biosynthesis , superpathway of tryptophan biosynthesis , chorismate biosynthesis I , chorismate biosynthesis from 3-dehydroquinate

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Citations: [Ely79, DeFeyter86a, DeFeyter86b, Millar86]

Cofactors or Prosthetic Groups: Mg2+ [DeFeyter86]

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+)

Kinetic Parameters:

Substrate
Km (μM)
Citations
shikimate
20000.0
[Pereira07, BRENDA14]
shikimate
5000.0, 200.0
[De87, BRENDA14]
shikimate
200.0
[DeFeyter86, BRENDA14]
ATP
160.0
[De87, BRENDA14]
ATP
160.0
[DeFeyter86, BRENDA14]


Sequence Features

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[DeFeyter86, Millar86, UniProt11a]
UniProt: Removed.
Chain 2 -> 174
[UniProt09]
UniProt: Shikimate kinase 2;
Nucleotide-Phosphate-Binding-Region 12 -> 17
[UniProt10]
UniProt: ATP; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 16
[UniProt10]
UniProt: Magnesium; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 32
[UniProt10]
UniProt: Magnesium; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 34
[UniProt10]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 58
[UniProt10]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 79
[UniProt10]
UniProt: Substrate; via amide nitrogen; Non-Experimental Qualifier: by similarity;
Protein-Segment 112 -> 126
[UniProt10]
UniProt: LID domain; Sequence Annotation Type: region of interest;
Amino-Acid-Sites-That-Bind 120
[UniProt10]
UniProt: ATP; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 139
[UniProt10]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;

History:
10/20/97 Gene b0388 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10082; confirmed by SwissProt match.


References

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

De87: De Feyter R (1987). "Shikimate kinases from Escherichia coli K12." Methods Enzymol 142;355-61. PMID: 3037263

DeFeyter86: DeFeyter RC, Pittard J (1986). "Purification and properties of shikimate kinase II from Escherichia coli K-12." J Bacteriol 1986;165(1);331-3. PMID: 3001029

DeFeyter86a: DeFeyter RC, Pittard J (1986). "Genetic and molecular analysis of aroL, the gene for shikimate kinase II in Escherichia coli K-12." J Bacteriol 1986;165(1);226-32. PMID: 3001024

DeFeyter86b: 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

Ely79: Ely B, Pittard J (1979). "Aromatic amino acid biosynthesis: regulation of shikimate kinase in Escherichia coli K-12." J Bacteriol 1979;138(3);933-43. PMID: 222728

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Lawley94: Lawley B, Pittard AJ (1994). "Regulation of aroL expression by TyrR protein and Trp repressor in Escherichia coli K-12." J Bacteriol 176(22);6921-30. PMID: 7961453

LobnerOlesen92: Lobner-Olesen A, Marinus MG (1992). "Identification of the gene (aroK) encoding shikimic acid kinase I of Escherichia coli." J Bacteriol 1992;174(2);525-9. PMID: 1309529

Millar86: 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

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Whipp95: Whipp MJ, Pittard AJ (1995). "A reassessment of the relationship between aroK- and aroL-encoded shikimate kinase enzymes of Escherichia coli." J Bacteriol 177(6);1627-9. PMID: 7883721


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC13B.