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.
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.
twitter

Escherichia coli K-12 substr. MG1655 Enzyme: aspartate aminotransferase, PLP-dependent



Gene: aspC Accession Numbers: EG10096 (EcoCyc), b0928, ECK0919

Regulation Summary Diagram: ?

Subunit composition of aspartate aminotransferase, PLP-dependent = [AspC]2

Summary:
Aspartate aminotransferase (AspC) is a multifunctional enzyme that catalyzes the synthesis of aspartate, phenylalanine, tyrosine and other compounds via a transamination reaction.

AspC catalyzes the synthesis of aspartate, phenylalanine, tyrosine and kynurenate [Fotheringham86, Gelfand77, Gelfand77a, Powell78, Bonner90, Chao99, Han01]. This reaction is catalyzed via a ping-pong Bi-Bi mechanism in which the cofactor alternates between the pyridoxal phosphate and pyridoxamine forms [Danishefsky91]. An amino acid substrate binds via an aldimine bond to pyridoxal phosphate, after which a hydrogen atom is removed from the substrate. This deprotonation yields a quinonoid intermediate, which is followed by addition of a proton to the coenzyme and the formation of a ketimine intermediate. This intermediate is then hydrolyzed to form a keto acid substrate and the pyridoxamine form of the enzyme. This reaction mechanism has been studied extensively [Malcolm85, Kuramitsu90, Planas91, Gloss95a, Birolo95, Goldberg96, Hayashi98, Mizuguchi01, Hayashi03, Islam03, Griswold12].

AspC is catalytically active as a dimer [Leistler92]. A crystal structure of AspC to 2.5 Å resolution showed that each of its subunits has a large and a small domain as well as one bound pyridoxal 5'-phosphate [Kamitori90]. Many crystal structures have been generated for AspC and mutant variants of AspC, in both bound and unbound states, usually to resolutions in the 2-3 Å range [Smith86, Smith89, Danishefsky91, Ziak93, Almo94, Jager94a, Jager94, Vacca95, Malashkevich95, Birolo99, Griswold11]. Crystal structures of AspC bound to inhibitors reveal that they operate by closing up the active site [Okamoto94]. In the case of maleate, this occurs after maleate itself occupies the active site [Miyahara94]. Structures of several cysteine mutants show that alteration of non-active-site residues can also affect the conformation of the active site [Jeffery00]. The active site has also been studied via NMR [Mollova97].

Additional crystal structures of recombinant AspC in complex with the mechanism-based inhibitor S-ADTA have been determined at different pH values. These studies led to the conclusions that inactivation by this compound can occur via two different mechanisms depending upon its binding direction, and that the protein structure itself is pH-dependent, which has mechanistic implications [Liu07]. Co-crystal structures with S-ADFA showed that the inhibitor formed an adduct with the active site lysine 264 [Liu10]. Note that in these publications and others (see below) some of the residue numbers given do not precisely match the locations of those residues in the current sequence for AspC, but they do refer to this protein.

A number of studies have looked at the residues around and in the active site, as well as their interaction with pyridoxal 5'-phosphate (note that some of the residue numbers given in these studies do not precisely match the locations of those residues in the current sequence for AspC, but they do refer to this protein) [Danishefsky91, Yano91, Toney91a, Inoue91, Yano92, Yano93a, Yano93, Goldberg93, Onuffer94, Matsushima94].

AspC can be mutated to alter its activity to that of a tyrosine transaminase of roughly equivalent efficacy [Malashkevich95a, Onuffer95, Rothman03, Rothman04, Chow04]. It has been mutated to develop other changes in substrate specificity as well [Graber95, Vacca97, Graber99, Fernandez12]. The specificity of AspC has even been altered by mutations in residues that are not a part of the active site [Oue99].

Denaturation studies have been used to investigate the unfolding pathway of this homodimeric enzyme in order to understand intersubunit interactions [Deu07a, Deu07]. Site-directed mutagenesis combined with denaturation studies have also investigated the role of side chain residues in intersubunit interactions. Multiple interactions were found to be involved in dimer stability. The active site on each monomer has components contributed by both monomers. Residues involved in catalysis and cofactor binding were also shown to be important to dimer stability [Deu09]. Allosteric communication between the two active sites has been shown [Deu11].

Review: [Hammes11]

Citations: [Kondo84, Kuramitsu85a, Kondo87, Toney91, Metzler94, Furumo95, Gloss95]

Locations: cytosol

Map Position: [983,742 <- 984,932] (21.2 centisomes)
Length: 1191 bp / 396 aa

Molecular Weight of Polypeptide: 43.573 kD (from nucleotide sequence)

pI: 5.8

Unification Links: ASAP:ABE-0003150 , CGSC:990 , DIP:DIP-9181N , EchoBASE:EB0094 , EcoGene:EG10096 , EcoliWiki:b0928 , ModBase:P00509 , OU-Microarray:b0928 , PortEco:aspC , PR:PRO_000022172 , Pride:P00509 , Protein Model Portal:P00509 , RefSeq:NP_415448 , RegulonDB:EG10096 , SMR:P00509 , String:511145.b0928 , UniProt:P00509

Relationship Links: InterPro:IN-FAMILY:IPR000796 , InterPro:IN-FAMILY:IPR004838 , InterPro:IN-FAMILY:IPR004839 , InterPro:IN-FAMILY:IPR015421 , InterPro:IN-FAMILY:IPR015424 , Panther:IN-FAMILY:PTHR11879 , PDB:Structure:1AAM , PDB:Structure:1AAW , PDB:Structure:1AHE , PDB:Structure:1AHF , PDB:Structure:1AHG , PDB:Structure:1AHX , PDB:Structure:1AHY , PDB:Structure:1AIA , PDB:Structure:1AIB , PDB:Structure:1AIC , PDB:Structure:1AMQ , PDB:Structure:1AMR , PDB:Structure:1AMS , PDB:Structure:1ARG , PDB:Structure:1ARH , PDB:Structure:1ARI , PDB:Structure:1ARS , PDB:Structure:1ART , PDB:Structure:1ASA , PDB:Structure:1ASB , PDB:Structure:1ASC , PDB:Structure:1ASD , PDB:Structure:1ASE , PDB:Structure:1ASF , PDB:Structure:1ASG , PDB:Structure:1ASL , PDB:Structure:1ASM , PDB:Structure:1ASN , PDB:Structure:1B4X , PDB:Structure:1BQA , PDB:Structure:1BQD , PDB:Structure:1C9C , PDB:Structure:1CQ6 , PDB:Structure:1CQ7 , PDB:Structure:1CQ8 , PDB:Structure:1CZC , PDB:Structure:1CZE , PDB:Structure:1G4V , PDB:Structure:1G4X , PDB:Structure:1G7W , PDB:Structure:1G7X , PDB:Structure:1IX6 , PDB:Structure:1IX7 , PDB:Structure:1IX8 , PDB:Structure:1QIR , PDB:Structure:1QIS , PDB:Structure:1QIT , PDB:Structure:1SPA , PDB:Structure:1TOE , PDB:Structure:1TOG , PDB:Structure:1TOI , PDB:Structure:1TOJ , PDB:Structure:1TOK , PDB:Structure:1X28 , PDB:Structure:1X29 , PDB:Structure:1X2A , PDB:Structure:1YOO , PDB:Structure:2AAT , PDB:Structure:2D5Y , PDB:Structure:2D7Y , PDB:Structure:2D7Z , PDB:Structure:2D61 , PDB:Structure:2D63 , PDB:Structure:2D64 , PDB:Structure:2D65 , PDB:Structure:2D66 , PDB:Structure:2Q7W , PDB:Structure:2QA3 , PDB:Structure:2QB2 , PDB:Structure:2QB3 , PDB:Structure:2QBT , PDB:Structure:3AAT , PDB:Structure:3QN6 , PDB:Structure:3QPG , PDB:Structure:3ZZJ , PDB:Structure:3ZZK , PDB:Structure:4A00 , PDB:Structure:4DBC , PDB:Structure:4F5F , PDB:Structure:4F5G , PDB:Structure:4F5H , PDB:Structure:4F5I , PDB:Structure:4F5J , PDB:Structure:4F5K , PDB:Structure:4F5L , PDB:Structure:4F5M , PDB:Structure:5EAA , Pfam:IN-FAMILY:PF00155 , Prints:IN-FAMILY:PR00799 , Prosite:IN-FAMILY:PS00105

Gene-Reaction Schematic: ?

Instance reaction of [an aromatic amino acid + 2-oxoglutarate ↔ an aromatic oxo-acid + L-glutamate] (2.6.1.57):
i1: L-tyrosine + 2-oxoglutarate ↔ 4-hydroxyphenylpyruvate + L-glutamate (2.6.1.5/2.6.1.57)

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0009094 - L-phenylalanine biosynthetic process Inferred from experiment [Gelfand77]
GO:0033585 - L-phenylalanine biosynthetic process from chorismate via phenylpyruvate Inferred from experiment [Gelfand77]
GO:0006520 - cellular amino acid metabolic process Inferred by computational analysis [GOA01a]
GO:0009058 - biosynthetic process Inferred by computational analysis [GOA01a]
Molecular Function: GO:0004069 - L-aspartate:2-oxoglutarate aminotransferase activity Inferred from experiment Inferred by computational analysis [GOA01, Gelfand77]
GO:0004838 - L-tyrosine:2-oxoglutarate aminotransferase activity Inferred from experiment [Gelfand77]
GO:0030170 - pyridoxal phosphate binding Inferred from experiment Inferred by computational analysis [GOA01a, Powell78]
GO:0042802 - identical protein binding Inferred from experiment [Rajagopala14, Lasserre06]
GO:0042803 - protein homodimerization activity Inferred from experiment [Powell78]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0008483 - transaminase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
GO:0080130 - L-phenylalanine:2-oxoglutarate aminotransferase activity Inferred by computational analysis [GOA01]
Cellular Component: GO:0005737 - cytoplasm Inferred from experiment Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, Powell78]
GO:0005829 - cytosol Inferred from experiment [Lasserre06]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids aspartate
metabolism carbon utilization amino acids

Essentiality data for aspC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Credits:
Curated 18-Jan-2007 by Shearer A , SRI International
Curated 14-Jan-2010 by Fulcher C , SRI International
Last-Curated ? 09-Jan-2013 by Keseler I , SRI International


Enzymatic reaction of: aspartate transaminase (aspartate aminotransferase, PLP-dependent)

Synonyms: aspartate aminotransferase, transaminase A (sic), glutamic-oxoaloacetic transaminase, glutamic-aspartic transaminase, tyrosine non-repressible aspartate aminotransferase, AspAT

EC Number: 2.6.1.1

L-aspartate + 2-oxoglutarate <=> oxaloacetate + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Powell78]

In Pathways: aspartate superpathway , superpathway of lysine, threonine and methionine biosynthesis I , superpathway of aspartate and asparagine biosynthesis; interconversion of aspartate and asparagine , threonine biosynthesis , aspartate biosynthesis , glutamate degradation II

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Powell78]

Cofactor Binding Comment: Aminotransferases almost without exception require pyridoxal 5'phosphate as a cofactor, which is covalently bound to the enzyme by the formation of a Schiff base with the E-amino group of a lysine residue [Fotheringham86].

Inhibitors (Allosteric): 2-methylaspartate [Okamoto94]

Inhibitors (Competitive): maleate [Miyahara94]

Inhibitors (Unknown Mechanism): (S)-4-amino-4,5-dihydro-2-thiophenecarboxylate [Liu07]


Enzymatic reaction of: phenylalanine transaminase (aspartate aminotransferase, PLP-dependent)

Synonyms: aromatic-amino-acid:2-oxoglutarate aminotransferase, aromatic aminotransferase, aromatic-amino-acid transaminase, phenylalanine aminotransferase

2-oxo-3-phenylpropanoate + L-glutamate <=> L-phenylalanine + 2-oxoglutarate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible. [Powell78]

Alternative Substrates for 2-oxo-3-phenylpropanoate: 4-hydroxyphenylpyruvate [Powell78 ]

In Pathways: superpathway of chorismate metabolism , superpathway of phenylalanine, tyrosine, and tryptophan biosynthesis , phenylalanine biosynthesis I

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Powell78]

Inhibitors (Allosteric): 2-methylaspartate [Okamoto94]

Inhibitors (Competitive): maleate [Miyahara94]

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
L-phenylalanine
8000.0
4.73
[Han01]


Enzymatic reaction of: tyrosine aminotransferase (aspartate aminotransferase, PLP-dependent)

Synonyms: aromatic-amino-acid:2-oxoglutarate aminotransferase, aromatic-amino-acid transaminase, aromatic aminotransferase

EC Number: 2.6.1.5

L-tyrosine + 2-oxoglutarate <=> 4-hydroxyphenylpyruvate + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Powell78]

In Pathways: superpathway of chorismate metabolism , superpathway of phenylalanine, tyrosine, and tryptophan biosynthesis , tyrosine biosynthesis I


Enzymatic reaction of: kynurenine-oxoglutarate transaminase (aspartate aminotransferase, PLP-dependent)

Synonyms: L-kynurenine:2-oxoglutarate aminotransferase, kynurenine aminotransferase

EC Number: 2.6.1.7

L-kynurenine + 2-oxoglutarate <=> L-glutamate + 4-(2-aminophenyl)-2,4-dioxobutanoate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible.

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Powell78]

Inhibitors (Allosteric): 2-methylaspartate [Okamoto94]

Inhibitors (Competitive): maleate [Miyahara94]

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
L-kynurenine
3000.0
0.83
[Han01]


Enzymatic reaction of: cysteine transaminase (aspartate aminotransferase, PLP-dependent)

EC Number: 2.6.1.3

2-oxoglutarate + L-cysteine <=> L-glutamate + 3-mercaptopyruvate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: hydrogen sulfide biosynthesis I


Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 34
[UniProt10a]
UniProt: Aspartate; via amide nitrogen;
Mutagenesis-Variant 65
[Inoue91, UniProt11a]
Alternate sequence: Y → S; UniProt: Slight changes in activity.
Alternate sequence: Y → F; UniProt: Slight changes in activity.
Amino-Acid-Sites-That-Bind 130
[UniProt10a]
UniProt: Aspartate;
Mutagenesis-Variant 133
[Yano91, UniProt11a]
Alternate sequence: H → N; UniProt: Decreases to 60% in maximum rate of the overall reactions in both directions.
Alternate sequence: H → A; UniProt: Slight increase in maximum velocity of the overall transamination reaction between aspartate and 2-oxoglutarate.
Amino-Acid-Sites-That-Bind 183
[UniProt10a]
UniProt: Aspartate;
N6-pyridoxal-phosphate-Lys-Modification 246
[Kondo87, UniProt11]
UniProt: N6-(pyridoxal phosphate)lysine.
Mutagenesis-Variant 280
[Mahon99, UniProt11a]
Alternate sequence: R → V; UniProt: Reduces first-order rate constant over 25000-fold.
Mutagenesis-Variant 374
[Danishefsky91, Mahon99, UniProt11a]
Alternate sequence: R → Y; UniProt: Second-order rate constants are reduced by >5 orders of magnitude.
Alternate sequence: R → F; UniProt: Second-order rate constants are reduced by >5 orders of magnitude.
Alternate sequence: R → A; UniProt: Reduces first-order rate constant about 10000-fold.
Amino-Acid-Sites-That-Bind 374
[UniProt10a]
UniProt: Aspartate;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b0928 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10096; confirmed by SwissProt match.


References

Almo94: Almo SC, Smith DL, Danishefsky AT, Ringe D (1994). "The structural basis for the altered substrate specificity of the R292D active site mutant of aspartate aminotransferase from E. coli." Protein Eng 7(3);405-12. PMID: 7909946

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

Birolo95: Birolo L, Sandmeier E, Christen P, John RA (1995). "The roles of Tyr70 and Tyr225 in aspartate aminotransferase assessed by analysing the effects of mutations on the multiple reactions of the substrate analogue serine o-sulphate." Eur J Biochem 232(3);859-64. PMID: 7588727

Birolo99: Birolo L, Malashkevich VN, Capitani G, De Luca F, Moretta A, Jansonius JN, Marino G (1999). "Functional and structural analysis of cis-proline mutants of Escherichia coli aspartate aminotransferase." Biochemistry 38(3);905-13. PMID: 9893985

Bonner90: Bonner CA, Fischer RS, Ahmad S, Jensen RA (1990). "Remnants of an ancient pathway to L-phenylalanine and L-tyrosine in enteric bacteria: evolutionary implications and biotechnological impact." Appl Environ Microbiol 56(12);3741-7. PMID: 2082822

Chao99: Chao YP, Lai ZJ, Chen P, Chern JT (1999). "Enhanced conversion rate of L-phenylalanine by coupling reactions of aminotransferases and phosphoenolpyruvate carboxykinase in Escherichia coli K-12." Biotechnol Prog 15(3);453-8. PMID: 10356262

Chow04: Chow MA, McElroy KE, Corbett KD, Berger JM, Kirsch JF (2004). "Narrowing substrate specificity in a directly evolved enzyme: the A293D mutant of aspartate aminotransferase." Biochemistry 43(40);12780-7. PMID: 15461450

Danishefsky91: Danishefsky AT, Onnufer JJ, Petsko GA, Ringe D (1991). "Activity and structure of the active-site mutants R386Y and R386F of Escherichia coli aspartate aminotransferase." Biochemistry 1991;30(7);1980-5. PMID: 1993208

Deu07: Deu E, Kirsch JF (2007). "Cofactor-directed reversible denaturation pathways: the cofactor-stabilized Escherichia coli aspartate aminotransferase homodimer unfolds through a pathway that differs from that of the apoenzyme." Biochemistry 46(19);5819-29. PMID: 17441730

Deu07a: Deu E, Kirsch JF (2007). "The unfolding pathway for Apo Escherichia coli aspartate aminotransferase is dependent on the choice of denaturant." Biochemistry 46(19);5810-8. PMID: 17425331

Deu09: Deu E, Dhoot J, Kirsch JF (2009). "The partially folded homodimeric intermediate of Escherichia coli aspartate aminotransferase contains a "molten interface" structure." Biochemistry 48(2);433-41. PMID: 19099423

Deu11: Deu E, Kirsch JF (2011). "Engineering homooligomeric proteins to detect weak intersite allosteric communication: aminotransferases, a case study." Protein Sci 20(12);1991-2003. PMID: 21936010

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Fernandez12: Fernandez FJ, de Vries D, Pena-Soler E, Coll M, Christen P, Gehring H, Vega MC (2012). "Structure and mechanism of a cysteine sulfinate desulfinase engineered on the aspartate aminotransferase scaffold." Biochim Biophys Acta 1824(2);339-49. PMID: 22138634

Fotheringham86: Fotheringham IG, Dacey SA, Taylor PP, Smith TJ, Hunter MG, Finlay ME, Primrose SB, Parker DM, Edwards RM (1986). "The cloning and sequence analysis of the aspC and tyrB genes from Escherichia coli K12. Comparison of the primary structures of the aspartate aminotransferase and aromatic aminotransferase of E. coli with those of the pig aspartate aminotransferase isoenzymes." Biochem J 1986;234(3);593-604. PMID: 3521591

Furumo95: Furumo NC, Kirsch JF (1995). "Accumulation of the quinonoid intermediate in the reaction catalyzed by aspartate aminotransferase with cysteine sulfinic acid." Arch Biochem Biophys 319(1);49-54. PMID: 7771805

Gelfand77: Gelfand DH, Steinberg RA (1977). "Escherichia coli mutants deficient in the aspartate and aromatic amino acid aminotransferases." J Bacteriol 1977;130(1);429-40. PMID: 15983

Gelfand77a: Gelfand DH, Rudo N (1977). "Mapping of the aspartate and aromatic amino acid aminotransferase genes tyrB and aspC." J Bacteriol 130(1);441-4. PMID: 323238

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

Gloss95: Gloss LM, Kirsch JF (1995). "Examining the structural and chemical flexibility of the active site base, Lys-258, of Escherichia coli aspartate aminotransferase by replacement with unnatural amino acids." Biochemistry 34(38);12323-32. PMID: 7547975

Gloss95a: Gloss LM, Kirsch JF (1995). "Use of site-directed mutagenesis and alternative substrates to assign the prototropic groups important to catalysis by Escherichia coli aspartate aminotransferase." Biochemistry 34(12);3999-4007. PMID: 7696265

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."

Goldberg93: Goldberg JM, Zheng J, Deng H, Chen YQ, Callender R, Kirsch JF (1993). "Structure of the complex between pyridoxal 5'-phosphate and the tyrosine 225 to phenylalanine mutant of Escherichia coli aspartate aminotransferase determined by isotope-edited classical Raman difference spectroscopy." Biochemistry 32(32);8092-7. PMID: 8347609

Goldberg96: Goldberg JM, Kirsch JF (1996). "The reaction catalyzed by Escherichia coli aspartate aminotransferase has multiple partially rate-determining steps, while that catalyzed by the Y225F mutant is dominated by ketimine hydrolysis." Biochemistry 35(16);5280-91. PMID: 8611515

Graber95: Graber R, Kasper P, Malashkevich VN, Sandmeier E, Berger P, Gehring H, Jansonius JN, Christen P (1995). "Changing the reaction specificity of a pyridoxal-5'-phosphate-dependent enzyme." Eur J Biochem 232(2);686-90. PMID: 7556224

Graber99: Graber R, Kasper P, Malashkevich VN, Strop P, Gehring H, Jansonius JN, Christen P (1999). "Conversion of aspartate aminotransferase into an L-aspartate beta-decarboxylase by a triple active-site mutation." J Biol Chem 274(44);31203-8. PMID: 10531314

Griswold11: Griswold WR, Fisher AJ, Toney MD (2011). "Crystal structures of aspartate aminotransferase reconstituted with 1-deazapyridoxal 5'-phosphate: internal aldimine and stable l-aspartate external aldimine." Biochemistry 50(26);5918-24. PMID: 21627105

Griswold12: Griswold WR, Castro JN, Fisher AJ, Toney MD (2012). "Ground-state electronic destabilization via hyperconjugation in aspartate aminotransferase." J Am Chem Soc 134(20);8436-8. PMID: 22551424

Hammes11: Hammes GG, Benkovic SJ, Hammes-Schiffer S (2011). "Flexibility, diversity, and cooperativity: pillars of enzyme catalysis." Biochemistry 50(48);10422-30. PMID: 22029278

Han01: Han Q, Fang J, Li J (2001). "Kynurenine aminotransferase and glutamine transaminase K of Escherichia coli: identity with aspartate aminotransferase." Biochem J 360(Pt 3);617-23. PMID: 11736651

Hayashi03: Hayashi H, Mizuguchi H, Miyahara I, Nakajima Y, Hirotsu K, Kagamiyama H (2003). "Conformational change in aspartate aminotransferase on substrate binding induces strain in the catalytic group and enhances catalysis." J Biol Chem 278(11);9481-8. PMID: 12488449

Hayashi98: Hayashi H, Mizuguchi H, Kagamiyama H (1998). "The imine-pyridine torsion of the pyridoxal 5'-phosphate Schiff base of aspartate aminotransferase lowers its pKa in the unliganded enzyme and is crucial for the successive increase in the pKa during catalysis." Biochemistry 37(43);15076-85. PMID: 9790670

Inoue91: Inoue K, Kuramitsu S, Okamoto A, Hirotsu K, Higuchi T, Kagamiyama H (1991). "Site-directed mutagenesis of Escherichia coli aspartate aminotransferase: role of Tyr70 in the catalytic processes." Biochemistry 1991;30(31);7796-801. PMID: 1868057

Islam03: Islam MM, Hayashi H, Kagamiyama H (2003). "Reaction of aspartate aminotransferase with C5-dicarboxylic acids: comparison with the reaction with C4-dicarboxylic acids." J Biochem (Tokyo) 134(2);277-85. PMID: 12966078

Jager94: Jager J, Moser M, Sauder U, Jansonius JN (1994). "Crystal structures of Escherichia coli aspartate aminotransferase in two conformations. Comparison of an unliganded open and two liganded closed forms." J Mol Biol 239(2);285-305. PMID: 8196059

Jager94a: Jager J, Pauptit RA, Sauder U, Jansonius JN (1994). "Three-dimensional structure of a mutant E. coli aspartate aminotransferase with increased enzymic activity." Protein Eng 7(5);605-12. PMID: 8073030

Jeffery00: Jeffery CJ, Gloss LM, Petsko GA, Ringe D (2000). "The role of residues outside the active site: structural basis for function of C191 mutants of Escherichia coli aspartate aminotransferase." Protein Eng 13(2);105-12. PMID: 10708649

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kamitori90: Kamitori S, Okamoto A, Hirotsu K, Higuchi T, Kuramitsu S, Kagamiyama H, Matsuura Y, Katsube Y (1990). "Three-dimensional structures of aspartate aminotransferase from Escherichia coli and its mutant enzyme at 2.5 A resolution." J Biochem (Tokyo) 1990;108(2);175-84. PMID: 2121725

Kondo84: Kondo K, Wakabayashi S, Yagi T, Kagamiyama H (1984). "The complete amino acid sequence of aspartate aminotransferase from Escherichia coli: sequence comparison with pig isoenzymes." Biochem Biophys Res Commun 122(1);62-7. PMID: 6378205

Kondo87: Kondo K, Wakabayashi S, Kagamiyama H (1987). "Structural studies on aspartate aminotransferase from Escherichia coli. Covalent structure." J Biol Chem 1987;262(18);8648-57. PMID: 3298240

Kuramitsu85a: Kuramitsu S, Okuno S, Ogawa T, Ogawa H, Kagamiyama H (1985). "Aspartate aminotransferase of Escherichia coli: nucleotide sequence of the aspC gene." J Biochem (Tokyo) 97(4);1259-62. PMID: 3897210

Kuramitsu90: Kuramitsu S, Hiromi K, Hayashi H, Morino Y, Kagamiyama H (1990). "Pre-steady-state kinetics of Escherichia coli aspartate aminotransferase catalyzed reactions and thermodynamic aspects of its substrate specificity." Biochemistry 1990;29(23);5469-76. PMID: 2201406

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

Leistler92: Leistler B, Herold M, Kirschner K (1992). "Collapsed intermediates in the reconstitution of dimeric aspartate aminotransferase from Escherichia coli." Eur J Biochem 205(2);603-11. PMID: 1572361

Liu07: Liu D, Pozharski E, Lepore BW, Fu M, Silverman RB, Petsko GA, Ringe D (2007). "Inactivation of Escherichia coli L-aspartate aminotransferase by (S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid reveals "a tale of two mechanisms"." Biochemistry 46(37);10517-27. PMID: 17713924

Liu10: Liu D, Pozharski E, Fu M, Silverman RB, Ringe D (2010). "Mechanism of inactivation of Escherichia coli aspartate aminotransferase by (S)-4-amino-4,5-dihydro-2-furancarboxylic acid." Biochemistry 49(49);10507-15. PMID: 21033689

Mahon99: Mahon MM, Graber R, Christen P, Malthouse JP (1999). "The aspartate aminotransferase-catalysed exchange of the alpha-protons of aspartate and glutamate: the effects of the R386A and R292V mutations on this exchange reaction." Biochim Biophys Acta 1434(1);191-201. PMID: 10556573

Malashkevich95: Malashkevich VN, Jager J, Ziak M, Sauder U, Gehring H, Christen P, Jansonius JN (1995). "Structural basis for the catalytic activity of aspartate aminotransferase K258H lacking the pyridoxal 5'-phosphate-binding lysine residue." Biochemistry 34(2);405-14. PMID: 7819232

Malashkevich95a: Malashkevich VN, Onuffer JJ, Kirsch JF, Jansonius JN (1995). "Alternating arginine-modulated substrate specificity in an engineered tyrosine aminotransferase." Nat Struct Biol 2(7);548-53. PMID: 7664122

Malcolm85: Malcolm BA, Kirsch JF (1985). "Site-directed mutagenesis of aspartate aminotransferase from E. coli." Biochem Biophys Res Commun 132(3);915-21. PMID: 3907632

Matsushima94: Matsushima Y, Kim DW, Yoshimura T, Kuramitsu S, Kagamiyama H, Esaki N, Soda K (1994). "Replacement of active-site lysine-239 of thermostable aspartate aminotransferase by S-(2-aminoethyl)cysteine: properties of the mutant enzyme." J Biochem (Tokyo) 115(1);108-12. PMID: 8188615

Metzler94: Metzler DE, Metzler CM, Scott RD, Mollova ET, Kagamiyama H, Yano T, Kuramitsu S, Hayashi H, Hirotsu K, Miyahara I (1994). "NMR studies of 1H resonances in the 10-18-ppm range for aspartate aminotransferase from Escherichia coli." J Biol Chem 269(45);28027-33. PMID: 7961737

Miyahara94: Miyahara I, Hirotsu K, Hayashi H, Kagamiyama H (1994). "X-ray crystallographic study of pyridoxamine 5'-phosphate-type aspartate aminotransferases from Escherichia coli in three forms." J Biochem (Tokyo) 116(5);1001-12. PMID: 7896726

Mizuguchi01: Mizuguchi H, Hayashi H, Okada K, Miyahara I, Hirotsu K, Kagamiyama H (2001). "Strain is more important than electrostatic interaction in controlling the pKa of the catalytic group in aspartate aminotransferase." Biochemistry 40(2);353-60. PMID: 11148029

Mollova97: Mollova ET, Metzler DE, Kintanar A, Kagamiyama H, Hayashi H, Hirotsu K, Miyahara I (1997). "Use of 1H-15N heteronuclear multiple-quantum coherence NMR spectroscopy to study the active site of aspartate aminotransferase." Biochemistry 36(3);615-25. PMID: 9012676

Okamoto94: Okamoto A, Higuchi T, Hirotsu K, Kuramitsu S, Kagamiyama H (1994). "X-ray crystallographic study of pyridoxal 5'-phosphate-type aspartate aminotransferases from Escherichia coli in open and closed form." J Biochem (Tokyo) 116(1);95-107. PMID: 7798192

Onuffer94: Onuffer JJ, Kirsch JF (1994). "Characterization of the apparent negative co-operativity induced in Escherichia coli aspartate aminotransferase by the replacement of Asp222 with alanine. Evidence for an extremely slow conformational change." Protein Eng 7(3);413-24. PMID: 8177890

Onuffer95: Onuffer JJ, Kirsch JF (1995). "Redesign of the substrate specificity of Escherichia coli aspartate aminotransferase to that of Escherichia coli tyrosine aminotransferase by homology modeling and site-directed mutagenesis." Protein Sci 4(9);1750-7. PMID: 8528073

Oue99: Oue S, Okamoto A, Yano T, Kagamiyama H (1999). "Redesigning the substrate specificity of an enzyme by cumulative effects of the mutations of non-active site residues." J Biol Chem 274(4);2344-9. PMID: 9891001

Planas91: Planas A, Kirsch JF (1991). "Reengineering the catalytic lysine of aspartate aminotransferase by chemical elaboration of a genetically introduced cysteine." Biochemistry 30(33);8268-76. PMID: 1907854

Powell78: Powell JT, Morrison JF (1978). "The purification and properties of the aspartate aminotransferase and aromatic-amino-acid aminotransferase from Escherichia coli." Eur J Biochem 1978;87(2);391-400. PMID: 352693

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

Rothman03: Rothman SC, Kirsch JF (2003). "How does an enzyme evolved in vitro compare to naturally occurring homologs possessing the targeted function? Tyrosine aminotransferase from aspartate aminotransferase." J Mol Biol 327(3);593-608. PMID: 12634055

Rothman04: Rothman SC, Voorhies M, Kirsch JF (2004). "Directed evolution relieves product inhibition and confers in vivo function to a rationally designed tyrosine aminotransferase." Protein Sci 13(3);763-72. PMID: 14767072

Shatalin11: Shatalin K, Shatalina E, Mironov A, Nudler E (2011). "H2S: a universal defense against antibiotics in bacteria." Science 334(6058);986-90. PMID: 22096201

Smith86: Smith DL, Ringe D, Finlayson WL, Kirsch JF (1986). "Preliminary X-ray data for aspartate aminotransferase from Escherichia coli." J Mol Biol 191(2);301-2. PMID: 3543379

Smith89: Smith DL, Almo SC, Toney MD, Ringe D (1989). "2.8-A-resolution crystal structure of an active-site mutant of aspartate aminotransferase from Escherichia coli." Biochemistry 1989;28(20);8161-7. PMID: 2513875

Toney91: Toney MD, Kirsch JF (1991). "Kinetics and equilibria for the reactions of coenzymes with wild type and the Y70F mutant of Escherichia coli aspartate aminotransferase." Biochemistry 30(30);7461-6. PMID: 1677270

Toney91a: Toney MD, Kirsch JF (1991). "Tyrosine 70 fine-tunes the catalytic efficiency of aspartate aminotransferase." Biochemistry 30(30);7456-61. PMID: 1677269

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-11 released on 2011-11-22 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."

Vacca95: Vacca RA, Christen P, Malashkevich VN, Jansonius JN, Sandmeier E (1995). "Substitution of apolar residues in the active site of aspartate aminotransferase by histidine. Effects on reaction and substrate specificity." Eur J Biochem 227(1-2);481-7. PMID: 7851426

Vacca97: Vacca RA, Giannattasio S, Graber R, Sandmeier E, Marra E, Christen P (1997). "Active-site Arg --> Lys substitutions alter reaction and substrate specificity of aspartate aminotransferase." J Biol Chem 272(35);21932-7. PMID: 9268327

Yano91: Yano T, Kuramitsu S, Tanase S, Morino Y, Hiromi K, Kagamiyama H (1991). "The role of His143 in the catalytic mechanism of Escherichia coli aspartate aminotransferase." J Biol Chem 1991;266(10);6079-85. PMID: 2007566

Yano92: Yano T, Kuramitsu S, Tanase S, Morino Y, Kagamiyama H (1992). "Role of Asp222 in the catalytic mechanism of Escherichia coli aspartate aminotransferase: the amino acid residue which enhances the function of the enzyme-bound coenzyme pyridoxal 5'-phosphate." Biochemistry 1992;31(25);5878-87. PMID: 1610831

Yano93: Yano T, Mizuno T, Kagamiyama H (1993). "A hydrogen-bonding network modulating enzyme function: asparagine-194 and tyrosine-225 of Escherichia coli aspartate aminotransferase." Biochemistry 32(7);1810-5. PMID: 8439541

Yano93a: Yano T, Hinoue Y, Chen VJ, Metzler DE, Miyahara I, Hirotsu K, Kagamiyama H (1993). "Role of an active site residue analyzed by combination of mutagenesis and coenzyme analog." J Mol Biol 234(4);1218-29. PMID: 8263922

Ziak93: Ziak M, Jager J, Malashkevich VN, Gehring H, Jaussi R, Jansonius JN, Christen P (1993). "Mutant aspartate aminotransferase (K258H) without pyridoxal-5'-phosphate-binding lysine residue. Structural and catalytic properties." Eur J Biochem 211(3);475-84. PMID: 8436109

Other References Related to Gene Regulation

Kumar11: Kumar R, Shimizu K (2011). "Transcriptional regulation of main metabolic pathways of cyoA, cydB, fnr, and fur gene knockout Escherichia coli in C-limited and N-limited aerobic continuous cultures." Microb Cell Fact 10;3. PMID: 21272324

Staden84: Staden R (1984). "Graphic methods to determine the function of nucleic acid sequences." Nucleic Acids Res 12(1 Pt 2);521-38. PMID: 6364040


Report Errors or Provide Feedback
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 Mon Dec 22, 2014, BIOCYC13B.