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Information on EC 1.2.1.11 - aspartate-semialdehyde dehydrogenase and Organism(s) Escherichia coli and UniProt Accession P0A9Q9
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1.2.1.11 aspartate-semialdehyde dehydrogenaseSpecify your search results
Word Map
- 1.2.1.11
- diaminopimelate
- aspartokinase
- dihydrodipicolinate
-
balanced-lethal
-
beta-aspartyl
- drug development
- medicine
- biotechnology
- pharmacology
- synthesis
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
asadh, aspartate semialdehyde dehydrogenase, aspartate-beta-semialdehyde dehydrogenase, aspartate-semialdehyde dehydrogenase, aspartate beta-semialdehyde dehydrogenase, asa dh, aspartic semialdehyde dehydrogenase, l-aspartate-beta-semialdehyde dehydrogenase, asd enzyme, ecasadh, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ASA dehydrogenase
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ASA DH
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ASADH
aspartate semialdehyde dehydrogenase
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aspartic beta-semialdehyde dehydrogenase
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aspartic semialdehyde dehydrogenase
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dehydrogenase, aspartate semialdehyde
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L-aspartate-beta-semialdehyde:NADP oxidoreductase (phosphorylating)
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ASADH
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH + H+
catalytic Cys135 is essential for activity
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Phosphorylation
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redox reaction
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oxidation
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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-, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
L-aspartate-4-semialdehyde:NADP+ oxidoreductase (phosphorylating)
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CAS REGISTRY NUMBER
COMMENTARY
9000-98-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-aspartate 4-semialdehyde + phosphate + NAD+
L-4-aspartyl phosphate + NADH + H+
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-
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r
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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r
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH + H+
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-
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r
beta-3-methylaspartyl phosphate + NADPH
beta-3-methylaspartate 4-semialdehyde + phosphate + NADP+
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-
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?
L-4-aspartyl phosphate + NADPH + H+
L-aspartate 4-semialdehyde + phosphate + NADP+
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r
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH + H+
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-
-
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r
L-aspartate-4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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reverse reaction: reductive dephosphorylation
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r
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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?
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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-
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?
L-4-aspartyl phosphate + NADPH
L-aspartate-4-semialdehyde + phosphate + NADP+
part of the biosynthetic aspartate pathway
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-
?
L-4-aspartyl phosphate + NADPH
L-aspartate-4-semialdehyde + phosphate + NADP+
reductive dephosphorylation
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?
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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-
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?
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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synthesis of threonine
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r
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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enzyme in pathway from L-aspartic acid to L-lysine, L-methionine, L-threonine and L-isoleucine
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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-
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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-
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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r
additional information
?
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the putative phosphate side contains arginine and a lysine that can provide electrostratic attraction to bind an oxyanion
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?
additional information
?
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maximum velocity with HAsO42- is 0.4 times that with HPO42-
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?
additional information
?
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the kinetic parameters with arsenate are comparable to those of phosphate, vanadate is an excellent substrate for the enzyme
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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-
?
L-4-aspartyl phosphate + NADPH
L-aspartate-4-semialdehyde + phosphate + NADP+
part of the biosynthetic aspartate pathway
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?
L-aspartate 4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH + H+
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r
L-4-aspartyl phosphate + NADPH + H+
L-aspartate 4-semialdehyde + phosphate + NADP+
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r
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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?
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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synthesis of threonine
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r
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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enzyme in pathway from L-aspartic acid to L-lysine, L-methionine, L-threonine and L-isoleucine
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
very low activity with the wild-type enzyme, but 44fold and 66fold higher activity with enzyme mutants Q350N and Q350N/H171A, respectively, compared to the wild-type
NADPH
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L-aspartate 4-semialdehyde dehydrogenase transfers the pro-S hydrogen from NADPH
additional information
cofactor modes of wild-type and mutant enzymes determined by molecular modeling
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additional information
-
cofactor modes of wild-type and mutant enzymes determined by molecular modeling
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additional information
-
NAD+: 0.1% or less the rate of reaction with NADP+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-2-amino-5-fluoro-4-oxo-5-phosphono-pentanoic acid
irreversible inhibition
3-Chloroacetylpyridine-adenine dinucleotide phosphate
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NADP+ and NADPH protect
D-Cystine
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70% inhibition at 0.01 mM, binds via the cysteine moiety covalently to the catalytic Cys135 of the enzyme, pH-dependent proces, optimal at pH 7.0-7.5, inhibition is reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione, no protection by aspartate-beta-semialdehyde, NADP+ or NADPH, inhibition mechanism and kinetics
DTNB
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reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
L-cystine
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complete inhibition at 0.01 mM, binds via the cysteine moiety covalently to the catalytic Cys135 of the enzyme, pH-dependent process, optimal at pH 7.0-7.5, inhibition is reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione, no protection by aspartate-beta-semialdehyde, NADP+ or NADPH, inhibition mechanism and kinetics
L-cystine diethyl ester
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68% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
L-cystine dimethyl ester
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67% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
L-cystine hydroxamate
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20% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
L-2-Amino-4-oxo-5-chloropentanoic acid
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L-aspartate 4-semialdehyde protects the enzyme against inactivation, both NADP+ and NADPH decrease the rate of inactivation
L-2-Amino-4-oxo-5-chloropentanoic acid
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substrate analogue, irreversible inactivation, pseudo-first-order kinetics
additional information
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no inhibition by N,N'-diacetyl-L-cystine, L-cystine di-beta-naphthylamide, disulfiram, N-acetyl-L-cystine, 2,2-dithiodipyridine, 4,4-dithiodipyridine, L- and D-cysteine, and oxidized and reduced coenzyme A
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.2
(S)-2-amino-5-fluoro-4-oxo-5-phosphono-pentanoic acid
0.2 M Tris, 1 mM EDTA, pH 8.6, 15 mM phosphate, 0.15 mM NADP+, 37°C
3.9
(S)-2-amino-5-phosphono-pent-4-ynoic acid
0.2 M Tris, 1 mM EDTA, pH 8.6, 15 mM phosphate, 0.15 mM NADP+, 37°C
0.04
3-Chloroacetylpyridine-adenine dinucleotide phosphate
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competitive inhibitor with respect to NADP+
additional information
additional information
-
inhibition kinetics at 21°C and pH 7.5
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
26
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K12 23631/pOP12 strain, minimal media plus N-formyllysine and tetracycline
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
the enzyme has a rate-limiting key function in the biosynthesis of amino acids L-threonine, L-lysine, and L-isoleucine from L-aspartate via L-homoserine
metabolism
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aspartate beta-semialdehyde dehydrogenase is a key enzyme in an essential amino acid biosynthetic pathway catalyzing the second reaction in the aspartate pathway
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
additional information
dimer
crystal structure, subdomain structure of subunits, open and closed enzyme forms
additional information
the asymmetric unit contains three subunits: one complete dimer and a monomer which comes from a dimer lying along the crystallographic 2fold axis
additional information
-
the asymmetric unit contains three subunits: one complete dimer and a monomer which comes from a dimer lying along the crystallographic 2fold axis
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in open and closed form, 30 mg/ml purified recombinant enzyme in 10 mM Tris, pH 7.4, 40 mM KCl, with equal volume of reservoir solution, 0.006 ml sitting drops by vapour diffusion utilizing micro-bridges, 20% v/v ethylene glycol, 4°C, X-ray diffraction structure determination and analysis at 1.95 A and 1.6 A resolution, respectively, modeling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A163S
site-directed mutagenesis, the mutant shows almost unaltered cofactor specificity compared to the wild-type enzyme
H171
site-directed mutagenesis, the mutant shows almost unaltered cofactor specificity compared to the wild-type enzyme
L351V
site-directed mutagenesis, the mutant shows unaltered cofactor specificity compared to the wild-type enzyme
Q350N
site-directed mutagenesis, the mutant shows 44fold increased activity with NAD+ compared to the wild-type enzyme and can also also utilize NADH efficiently. Unlike the wild-type enzyme, mutants Q350N and Q350N/H171A are able to synthesize L-homoserine from aspartate efficiently with NADH as a cofactor
Q350N/H171A Q350N
site-directed mutagenesis, the mutant shows 66fold increased activity with NAD+ compared to the wild-type enzyme and can also utilize NADH efficiently. Unlike the wild-type enzyme, mutants Q350N and Q350N/H171A are able to synthesize L-homoserine from aspartate efficiently with NADH as a cofactor
S138Q
site-directed mutagenesis, the mutant shows unaltered cofactor specificity compared to the wild-type enzyme
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
lyophilization of purified or partially purified enzyme, slight loss of activity
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 10 mM potassium phosphate, pH 7.2, 0.1 mM EDTA, 1 mM dithioerythritol, 50% glycerol, 2 months
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4°C, 10 mM potassium phosphate, pH 7.2, 0.1 mM EDTA, 1 mM dithioerythritol, several days
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutants from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
K-12, using ammonium sulfate precipitation and column chromatography on Sephadex G-200 and DEAE-Sephadex A-50
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using column chromatography on DEAE-cellulose, DEAE-Sephadex A-50, hydroxylapatite, ultrogel ACA-44 and Sepharose C3
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using heat treatment, column chromatography on DEAE-cellulose, ammonium sulfate precipitation and column chromatography on Sephadex G-200
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene asd, construction of a genetic ecASADH library by saturation mutagenesis, recombinant expression of His-tagged wild-type and selected mutants in Escherichia coli strain BL21(DE3)
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
the modofied enzyme with altered substrate specificity using NAD(H) is preferred in biotechnological production of amino acids due to lower costs and higher stability
synthesis
the modofied enzyme with altered substrate specificity using NAD(H) is preferred in biotechnological production of amino acids due to lower costs and higher stability
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shames, S.L.; Ash, D.E.; Wedler, F.C.; Villafranca, J.J.
Interaction of aspartate and aspartate-derived antimetabolites with the enzymes of the threonine biosynthetic pathway of Escherichia coli
J. Biol. Chem.
259
15331-15339
1984
Escherichia coli
Hegeman, G.D.; Cohen, G.N.; Morgan, R.
Aspartic semialdehyde dehydrogenase (Escherichia coli K12)
Methods Enzymol.
17A
708-713
1970
Escherichia coli
-
Cohen, G.N.
Aspartate-semialdehyde dehydrogenase from Escherichia coli
Methods Enzymol.
113
600-602
1985
Escherichia coli
Biellmann, J.F.; Eid, P.; Hirth, C.; Jrnvall, H.
Aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. Purification and general properties
Eur. J. Biochem.
104
53-58
1980
Escherichia coli
Bielmann, J.F.; Eid, P.; Hirth, C.
Affinity labeling of the Escherichia coli aspartate-beta-semialdehyde dehydrogenase with an alkylating coenzyme analogue. Half-site reactivity and competition with the substrate alkylating analogue
Eur. J. Biochem.
104
65-69
1980
Escherichia coli
Biellmann, J.F.; Eid, P.; Hirth, C.; Jrnvall, H.
Aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. Affinity labeling with the substrate analogue L-2-amino-4-oxo-5-chloropentanoic acid: an example of half-site reactivity
Eur. J. Biochem.
104
59-64
1980
Escherichia coli
Preiss, J.; Mazelis, M.; Greenberg, E.
Cloning of the aspartate-beta-semialdehyde dehydrogenase structural gene from Escherichia coli K12
Curr. Microbiol.
7
263-268
1982
Escherichia coli
-
Hadfield, A.; Kryger, G.; Ouyang, J.; Petsko, G.A.; Ringe, D.; Viola, R.
Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis
J. Mol. Biol.
289
991-1002
1999
Escherichia coli (P0A9Q9), Escherichia coli
Kish, M.M.; Viola, R.E.
Oxyanion specificity of L-Aspartate-beta-semialdehyde dehydrogenase
Inorg. Chem.
38
818-820
1999
Escherichia coli
Alvarez, E.; Ramon, F.; Magan, C.; Diez, E.
L-cystine inhibits aspartate-beta-semialdehyde dehydrogenase by covalently binding to the essential 135Cys of the enzyme
Biochim. Biophys. Acta
1696
23-29
2004
Escherichia coli
Nichols, C.E.; Dhaliwal, B.; Lockyer, M.; Hawkins, A.R.; Stammers, D.K.
High-resolution structures reveal details of domain closure and "half-of-sites-reactivity" in Escherichia coli aspartate beta-semialdehyde dehydrogenase
J. Mol. Biol.
341
797-806
2004
Escherichia coli (P0A9Q9), Escherichia coli
Cox, R.J.; Gibson, J.S.; Hadfield, A.T.
Design, synthesis and analysis of inhibitors of bacterial aspartate semialdehyde dehydrogenase
ChemBiochem
6
2255-2260
2005
Bacteria, Escherichia coli (P0A9Q9)
Viola, R.E.; Faehnle, C.R.; Blanco, J.; Moore, R.A.; Liu, X.; Arachea, B.T.; Pavlovsky, A.G.
The catalytic machinery of a key enzyme in amino acid biosynthesis
J. Amino Acids
2011
352538
2011
Candida albicans, Streptococcus pneumoniae, Escherichia coli, Methanocaldococcus jannaschii, Haemophilus influenzae (P44801), Vibrio cholerae (Q9KQG2)
Xu, X.; Chen, J.; Wang, Q.; Duan, C.; Li, Y.; Wang, R.; Yang, S.
Mutagenesis of key residues in the binding center of L-aspartate-beta-semialdehyde dehydrogenase from Escherichia coli enhances utilization of the cofactor NAD(H)
ChemBioChem
17
56-64
2016
Escherichia coli (P0A9Q9), Escherichia coli
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