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Escherichia coli K-12 substr. MG1655 Enzyme: 4-hydroxy-tetrahydrodipicolinate synthase



Gene: dapA Accession Numbers: EG10205 (EcoCyc), b2478, ECK2474

Synonyms: DHDPS, dihydrodipicolinate synthase

Regulation Summary Diagram: ?

Subunit composition of 4-hydroxy-tetrahydrodipicolinate synthase = [DapA]4
         4-hydroxy-tetrahydrodipicolinate synthase = DapA

Summary:
4-Hydroxy-tetrahydrodipicolinate synthase, historically called dihydrodipicolinate synthase (DHDPS, DapA) is the first enzyme unique to lysine biosynthesis, catalyzing the condensation of pyruvate and (S)-aspartate β-semialdehyde. This is thought to be the rate-limiting step in lysine biosynthesis after aspartate kinase III [Laber92]. The product of the reaction catalyzed by DapA was identified as (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate (HTPA) [Blickling97].

The reaction proceeds via a ping-pong bi-bi mechanism; pyruvate initially binds to the enzyme via a Schiff base to the ε-amino group of the active site Lys161 residue [Laber92]. This is followed by addition of L-aspartate semialdehyde and transimination leading to cyclization and dissociation of HTPA [Blickling97]. The kinetic mechanism was refined using initial velocity and dead-end inhibition studies at both high and low pH, confirming the ping-pong reaction mechanism of the enzyme [Karsten97]. Surprisingly, Lys161 is not absolutely essential for catalysis [Soares10].

Crystal structures of the apo-enzyme and in complexes with substrates, substrate analogs and inhibitors, as well as of mutant enzymes have been solved [Mirwaldt95, Blickling97, Dobson04b, Dobson05, Dobson05a, Griffin08, Dobson08, Pearce08, Devenish08, Dobson09, Soares10, Boughton12]. DapA is a homotetramer that can be characterized as a dimer of dimers; each monomer consists of an N-terminal (β/α)8-barrel domain and three C-terminal α-helices. Site-directed mutants in the catalytic triad residues Tyr133, Thr44 and Tyr107 provided evidence for their functional importance [Dobson04b, Dobson09]. Arg138 plays a role in substrate binding [Dobson05a], and Ile203 may play a role in catalysis [Dobson08]. Although the active site of a dimeric variant of DapA is not disturbed, it shows reduced activity [Griffin08]. A Y107W mutant exists as a mixture of monomers and tetramers in solution and has reduced catalytic activity [Pearce08], and a L197D/Y107W double mutant is monomeric, has reduced catalytic efficiency and is not inhibited by lysine [MuscroftTaylor10a]. Molecular dynamics simulations indicate that the tetrameric form is relatively rigid, while the dimeric form is more flexible and shows disorder in the active site [Reboul12]. The C-terminal domain is required for maintenance of quarternary structure of the enzyme and thus for catalysis [Guo09]. The chaperone GroE appears to be required for folding of DapA [McLennan98].

Inhibition of enzyme activity by lysine was investigated by site-directed mutagenesis of predicted lysine binding residues [Geng13].

Transcription of dapA increases in response to diaminopimelic acid limitation [Acord04].

DapA: "diaminopimelate biosynthesis A" [Bukhari71]

Citations: [TruffaBachi67]

Gene Citations: [Bouvier91]

Locations: cytosol

Map Position: [2,596,904 <- 2,597,782] (55.97 centisomes)
Length: 879 bp / 292 aa

Molecular Weight of Polypeptide: 31.27 kD (from nucleotide sequence), 32.0 kD (experimental) [Laber92 ]

Molecular Weight of Multimer: 140.0 kD (experimental) [Borthwick95]

pI: 6.22

Unification Links: ASAP:ABE-0008163 , CGSC:880 , EchoBASE:EB0201 , EcoGene:EG10205 , EcoliWiki:b2478 , ModBase:P0A6L2 , OU-Microarray:b2478 , PortEco:dapA , PR:PRO_000022400 , Pride:P0A6L2 , Protein Model Portal:P0A6L2 , RefSeq:NP_416973 , RegulonDB:EG10205 , SMR:P0A6L2 , String:511145.b2478 , UniProt:P0A6L2

Relationship Links: InterPro:IN-FAMILY:IPR002220 , InterPro:IN-FAMILY:IPR005263 , InterPro:IN-FAMILY:IPR013785 , InterPro:IN-FAMILY:IPR020624 , InterPro:IN-FAMILY:IPR020625 , Panther:IN-FAMILY:PTHR12128 , PDB:Structure:1DHP , PDB:Structure:1S5T , PDB:Structure:1S5V , PDB:Structure:1S5W , PDB:Structure:1YXC , PDB:Structure:1YXD , PDB:Structure:2A6L , PDB:Structure:2A6N , PDB:Structure:2ATS , PDB:Structure:2OJP , PDB:Structure:2PUR , PDB:Structure:3C0J , PDB:Structure:3DEN , PDB:Structure:3DU0 , PDB:Structure:3I7Q , PDB:Structure:3I7R , PDB:Structure:3I7S , PDB:Structure:4EOU , Pfam:IN-FAMILY:PF00701 , Prints:IN-FAMILY:PR00146 , Prosite:IN-FAMILY:PS00665 , Prosite:IN-FAMILY:PS00666

In Paralogous Gene Group: 81 (7 members)

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0019877 - diaminopimelate biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA06, Bukhari71, Shedlarski70]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11]
GO:0009085 - lysine biosynthetic process Inferred by computational analysis [UniProtGOA11]
GO:0009089 - lysine biosynthetic process via diaminopimelate Inferred by computational analysis [UniProtGOA12, GOA01]
Molecular Function: GO:0008840 - 4-hydroxy-tetrahydrodipicolinate synthase Inferred from experiment Inferred by computational analysis [GOA01a, GOA01, Blickling97, Laber92, Shedlarski70]
GO:0042802 - identical protein binding Inferred from experiment [Rajagopala14, Lasserre06, Borthwick95]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0016843 - amine-lyase activity Inferred by computational analysis [GOA06]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05, Lasserre06]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, GOA06]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids lysine

Essentiality data for dapA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 1]

Credits:
Last-Curated ? 27-Feb-2013 by Keseler I , SRI International


Enzymatic reaction of: 4-hydroxy-tetrahydrodipicolinate synthase

Synonyms: HTPA synthase

EC Number: 4.3.3.7

pyruvate + L-aspartate-semialdehyde <=> (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O + H+

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 irreversible in the direction shown. [Karsten97]

Alternative Substrates for pyruvate: hydroxypyruvate [Devenish10 ]

In Pathways: aspartate superpathway , superpathway of lysine, threonine and methionine biosynthesis I , lysine biosynthesis I

Summary:
The enzyme was initially purified from E. coli W [Shedlarski70].

(S)-lysine is a mixed inhibitor and has an effect on the initial steps of the reaction, including pyruvate binding and Schiff base formation [Dobson04]. Lysine binding is cooperative [Blickling97].

(R)-ASA is neither a substrate nor an inhibitor of the enzyme [Dobson04a].

Citations: [Turner05a, Boughton12a]

Inhibitors (Competitive): dipicolinate (Kic = 11000µM) [Laber92, Karsten97] , succinate semialdehyde (Kic = 300µM) [Blickling97, Karsten97] , 3-bromopyruvate (Kic = 1600µM) [Laber92, Borthwick95]

Inhibitors (Mixed): L-lysine [Dobson04, Karsten97, Laber92, Richaud86]

Inhibitors (Irreversible): 2-oxopimelate [Blickling97]

Inhibitors (Unknown Mechanism): hydroxypyruvate [Dobson08] , S-(2-aminoethyl)-L-cysteine [Laber92]

Primary Physiological Regulators of Enzyme Activity: L-lysine

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
L-aspartate-semialdehyde
130.0
[Griffin10, BRENDA14]
L-aspartate-semialdehyde
110.0
[Devenish09, BRENDA14]
L-aspartate-semialdehyde
140.0
[Turner05, BRENDA14]
L-aspartate-semialdehyde
230.0, 290.0
[Guo09, BRENDA14]
L-aspartate-semialdehyde
111.0
[Dobson04a]
L-aspartate-semialdehyde
223.0
[Shedlarski70, BRENDA14]
pyruvate
380.0
[Turner05, BRENDA14]
pyruvate
260.0
[Pearce08, BRENDA14]
pyruvate
260.0
[Dobson04, BRENDA14]
pyruvate
260.0
[Devenish09, BRENDA14]
pyruvate
250.0, 300.0, 260.0
[Dobson04a, BRENDA14]
pyruvate
160.0
78.0
[Griffin10, BRENDA14]
pyruvate
9.8
[MuscroftTaylor10a, BRENDA14]
pyruvate
150.0
45.0
[Soares10, BRENDA14]
pyruvate
360.0, 370.0
1.2, 75.0
[Guo09, BRENDA14]
pyruvate
260.0
124.0
[Dobson04b, BRENDA14]


Sequence Features

Feature Class Location Citations Comment
Mutagenesis-Variant 44
[Dobson09, Dobson04b, UniProt13]
Alternate sequence: T → V; UniProt: Reduced kcat by 99.9%.
Alternate sequence: T → S; UniProt: 8% of wild-type activity. 4-fold decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA.
Amino-Acid-Site 44
[UniProt13]
UniProt: Part of a proton relay during catalysis; Sequence Annotation Type: site.
Amino-Acid-Sites-That-Bind 45
[UniProt13]
UniProt: Pyruvate.
Amino-Acid-Site 49
[UniProt13]
UniProt: L-lysine inhibitor binding; via carbonyl oxygen; Sequence Annotation Type: site.
Amino-Acid-Site 80
[UniProt13]
UniProt: L-lysine inhibitor binding; Sequence Annotation Type: site.
Amino-Acid-Site 84
[UniProt13]
UniProt: L-lysine inhibitor binding; Sequence Annotation Type: site.
Amino-Acid-Sites-That-Bind 106
[UniProt10]
UniProt: Pyruvate;
Mutagenesis-Variant 107
[Pearce08, Dobson04b, UniProt13]
Alternate sequence: Y → W; UniProt: Reduced activity by 95%. Reduced affinity for both substrates. Exists as a mixture of monomer, dimer and tetramer in solution. Has significantly lower thermal stability than the wild-type enzyme.
Alternate sequence: Y → F; UniProt: Reduced kcat by 90%.
Amino-Acid-Site 107
[UniProt13]
UniProt: Part of a proton relay during catalysis; Sequence Annotation Type: site.
Mutagenesis-Variant 133
[Dobson04b, UniProt13]
Alternate sequence: Y → F; UniProt: Reduced kcat by 99.7%. Reduced affinity for both substrates.
Active-Site 133
[Dobson09, Laber92, UniProt13]
UniProt: Proton donor/acceptor.
Mutagenesis-Variant 138
[Dobson05a, UniProt13]
Alternate sequence: R → H; UniProt: Strongly increased KM for L- aspartate 4-semialdehyde. No effect on KM for pyruvate. Reduced activity by 99.7%.
Alternate sequence: R → A; UniProt: Strongly increased KM for L- aspartate 4-semialdehyde. No effect on KM for pyruvate. Reduced activity by 99.7%.
Mutagenesis-Variant 161
[Soares10, UniProt13]
Alternate sequence: K → R; UniProt: 0.35% of wild-type activity. 3-fold decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA.
Alternate sequence: K → A; UniProt: 0.1% of wild-type activity. 3-fold decrease in affinity for pyruvate, and 2- fold decrease in that for (S)-ASA.
Active-Site 161
[Dobson09, Laber92, UniProt13]
UniProt: Schiff-base intermediate with substrate.
Mutagenesis-Variant 197
[Griffin08, UniProt13]
Alternate sequence: L → D; UniProt: 1.4 to 2.5% of wild-type activity. Decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. Exists as a dimer in solution.
Alternate sequence: L → Y; UniProt: 1.4 to 2.5% of wild-type activity. Decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. Exists as a dimer in solution.
Amino-Acid-Sites-That-Bind 203
[UniProt13]
UniProt: Pyruvate; via carbonyl oxygen.
Sequence-Conflict 207
[Richaud86, UniProt10]
Alternate sequence: A → T; UniProt: (in Ref. 1; AAA23665);
Sequence-Conflict 224
[Richaud86, UniProt10]
Alternate sequence: G → E; UniProt: (in Ref. 1; AAA23665);


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b2478 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10205; confirmed by SwissProt match.


References

Acord04: Acord J, Masters M (2004). "Expression from the Escherichia coli dapA promoter is regulated by intracellular levels of diaminopimelic acid." FEMS Microbiol Lett 235(1);131-7. PMID: 15158272

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

Blickling97: Blickling S, Renner C, Laber B, Pohlenz HD, Holak TA, Huber R (1997). "Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated by X-ray crystallography and NMR spectroscopy." Biochemistry 36(1);24-33. PMID: 8993314

Borthwick95: Borthwick EB, Connell SJ, Tudor DW, Robins DJ, Shneier A, Abell C, Coggins JR (1995). "Escherichia coli dihydrodipicolinate synthase: characterization of the imine intermediate and the product of bromopyruvate treatment by electrospray mass spectrometry." Biochem J 305 ( Pt 2);521-4. PMID: 7832769

Boughton12: Boughton BA, Dobson RC, Hutton CA (2012). "The crystal structure of dihydrodipicolinate synthase from Escherichia coli with bound pyruvate and succinic acid semialdehyde: unambiguous resolution of the stereochemistry of the condensation product." Proteins 80(8);2117-22. PMID: 22552955

Boughton12a: Boughton BA, Hor L, Gerrard JA, Hutton CA (2012). "1,3-Phenylene bis(ketoacid) derivatives as inhibitors of Escherichia coli dihydrodipicolinate synthase." Bioorg Med Chem 20(7);2419-26. PMID: 22386717

Bouvier91: Bouvier J, Pugsley AP, Stragier P (1991). "A gene for a new lipoprotein in the dapA-purC interval of the Escherichia coli chromosome." J Bacteriol 1991;173(17);5523-31. PMID: 1885529

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

Bukhari71: Bukhari AI, Taylor AL (1971). "Genetic analysis of diaminopimelic acid- and lysine-requiring mutants of Escherichia coli." J Bacteriol 105(3);844-54. PMID: 4926684

Devenish08: Devenish SR, Gerrard JA, Jameson GB, Dobson RC (2008). "The high-resolution structure of dihydrodipicolinate synthase from Escherichia coli bound to its first substrate, pyruvate." Acta Crystallogr Sect F Struct Biol Cryst Commun 64(Pt 12);1092-5. PMID: 19052357

Devenish09: Devenish SR, Huisman FH, Parker EJ, Hadfield AT, Gerrard JA (2009). "Cloning and characterisation of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis." Biochim Biophys Acta 1794(8);1168-74. PMID: 19236959

Devenish10: Devenish SR, Blunt JW, Gerrard JA (2010). "NMR studies uncover alternate substrates for dihydrodipicolinate synthase and suggest that dihydrodipicolinate reductase is also a dehydratase." J Med Chem 53(12);4808-12. PMID: 20503968

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

Dobson04: Dobson RC, Griffin MD, Roberts SJ, Gerrard JA (2004). "Dihydrodipicolinate synthase (DHDPS) from Escherichia coli displays partial mixed inhibition with respect to its first substrate, pyruvate." Biochimie 86(4-5);311-5. PMID: 15194235

Dobson04a: Dobson RC, Gerrard JA, Pearce FG (2004). "Dihydrodipicolinate synthase is not inhibited by its substrate, (S)-aspartate beta-semialdehyde." Biochem J 377(Pt 3);757-62. PMID: 14580236

Dobson04b: Dobson RC, Valegard K, Gerrard JA (2004). "The crystal structure of three site-directed mutants of Escherichia coli dihydrodipicolinate synthase: further evidence for a catalytic triad." J Mol Biol 338(2);329-39. PMID: 15066435

Dobson05: Dobson RC, Griffin MD, Jameson GB, Gerrard JA (2005). "The crystal structures of native and (S)-lysine-bound dihydrodipicolinate synthase from Escherichia coli with improved resolution show new features of biological significance." Acta Crystallogr D Biol Crystallogr 61(Pt 8);1116-24. PMID: 16041077

Dobson05a: Dobson RC, Devenish SR, Turner LA, Clifford VR, Pearce FG, Jameson GB, Gerrard JA (2005). "Role of arginine 138 in the catalysis and regulation of Escherichia coli dihydrodipicolinate synthase." Biochemistry 44(39);13007-13. PMID: 16185069

Dobson08: Dobson RC, Griffin MD, Devenish SR, Pearce FG, Hutton CA, Gerrard JA, Jameson GB, Perugini MA (2008). "Conserved main-chain peptide distortions: a proposed role for Ile203 in catalysis by dihydrodipicolinate synthase." Protein Sci 17(12);2080-90. PMID: 18787203

Dobson09: Dobson RC, Perugini MA, Jameson GB, Gerrard JA (2009). "Specificity versus catalytic potency: The role of threonine 44 in Escherichia coli dihydrodipicolinate synthase mediated catalysis." Biochimie 91(8);1036-44. PMID: 19505526

Geng13: Geng F, Chen Z, Zheng P, Sun J, Zeng AP (2013). "Exploring the allosteric mechanism of dihydrodipicolinate synthase by reverse engineering of the allosteric inhibitor binding sites and its application for lysine production." Appl Microbiol Biotechnol 97(5);1963-71. PMID: 22644522

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

Griffin08: Griffin MD, Dobson RC, Pearce FG, Antonio L, Whitten AE, Liew CK, Mackay JP, Trewhella J, Jameson GB, Perugini MA, Gerrard JA (2008). "Evolution of quaternary structure in a homotetrameric enzyme." J Mol Biol 380(4);691-703. PMID: 18556019

Griffin10: Griffin MD, Dobson RC, Gerrard JA, Perugini MA (2010). "Exploring the dihydrodipicolinate synthase tetramer: how resilient is the dimer-dimer interface?." Arch Biochem Biophys 494(1);58-63. PMID: 19919824

Guo09: Guo BB, Devenish SR, Dobson RC, Muscroft-Taylor AC, Gerrard JA (2009). "The C-terminal domain of Escherichia coli dihydrodipicolinate synthase (DHDPS) is essential for maintenance of quaternary structure and efficient catalysis." Biochem Biophys Res Commun 380(4);802-6. PMID: 19338756

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Karsten97: Karsten WE (1997). "Dihydrodipicolinate synthase from Escherichia coli: pH dependent changes in the kinetic mechanism and kinetic mechanism of allosteric inhibition by L-lysine." Biochemistry 36(7);1730-9. PMID: 9048556

Laber92: Laber B, Gomis-Ruth FX, Romao MJ, Huber R (1992). "Escherichia coli dihydrodipicolinate synthase. Identification of the active site and crystallization." Biochem J 1992;288 ( Pt 2);691-5. PMID: 1463470

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

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

McLennan98: McLennan N, Masters M (1998). "GroE is vital for cell-wall synthesis." Nature 392(6672);139. PMID: 9515958

Mirwaldt95: Mirwaldt C, Korndorfer I, Huber R (1995). "The crystal structure of dihydrodipicolinate synthase from Escherichia coli at 2.5 A resolution." J Mol Biol 246(1);227-39. PMID: 7853400

MuscroftTaylor10: Muscroft-Taylor AC, Soares da Costa TP, Gerrard JA (2010). "New insights into the mechanism of dihydrodipicolinate synthase using isothermal titration calorimetry." Biochimie 92(3);254-62. PMID: 20025926

MuscroftTaylor10a: Muscroft-Taylor AC, Catchpole RJ, Dobson RC, Pearce FG, Perugini MA, Gerrard JA (2010). "Disruption of quaternary structure in Escherichia coli dihydrodipicolinate synthase (DHDPS) generates a functional monomer that is no longer inhibited by lysine." Arch Biochem Biophys 503(2);202-6. PMID: 20709017

Pearce08: Pearce FG, Dobson RC, Weber A, Lane LA, McCammon MG, Squire MA, Perugini MA, Jameson GB, Robinson CV, Gerrard JA (2008). "Mutating the tight-dimer interface of dihydrodipicolinate synthase disrupts the enzyme quaternary structure: toward a monomeric enzyme." Biochemistry 47(46);12108-17. PMID: 18937497

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Reboul12: Reboul CF, Porebski BT, Griffin MD, Dobson RC, Perugini MA, Gerrard JA, Buckle AM (2012). "Structural and dynamic requirements for optimal activity of the essential bacterial enzyme dihydrodipicolinate synthase." PLoS Comput Biol 8(6);e1002537. PMID: 22685390

Richaud86: Richaud F, Richaud C, Ratet P, Patte JC (1986). "Chromosomal location and nucleotide sequence of the Escherichia coli dapA gene." J Bacteriol 1986;166(1);297-300. PMID: 3514578

Shedlarski70: Shedlarski JG, Gilvarg C (1970). "The pyruvate-aspartic semialdehyde condensing enzyme of Escherichia coli." J Biol Chem 1970;245(6);1362-73. PMID: 4910051

Soares10: Soares da Costa TP, Muscroft-Taylor AC, Dobson RC, Devenish SR, Jameson GB, Gerrard JA (2010). "How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase?." Biochimie 92(7);837-45. PMID: 20353808

TruffaBachi67: Truffa-Bachi P, Patte JC, Cohen GN (1967). "[On the dihydrodipicolinate synthetase of Escherichia coli K12]." C R Acad Sci Hebd Seances Acad Sci D 265(13);928-9. PMID: 4967862

Turner05: Turner JJ, Gerrard JA, Hutton CA (2005). "Heterocyclic inhibitors of dihydrodipicolinate synthase are not competitive." Bioorg Med Chem 13(6);2133-40. PMID: 15727866

Turner05a: Turner JJ, Healy JP, Dobson RC, Gerrard JA, Hutton CA (2005). "Two new irreversible inhibitors of dihydrodipicolinate synthase: diethyl (E,E)-4-oxo-2,5-heptadienedioate and diethyl (E)-4-oxo-2-heptenedioate." Bioorg Med Chem Lett 15(4);995-8. PMID: 15686899

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

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

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

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

Other References Related to Gene Regulation

Jovanovic03: Jovanovic M, Lilic M, Savic DJ, Jovanovic G (2003). "The LysR-type transcriptional regulator CysB controls the repression of hslJ transcription in Escherichia coli." Microbiology 149(Pt 12);3449-59. PMID: 14663078


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Tue Nov 25, 2014, biocyc14.