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Information on EC 1.2.1.11 - aspartate-semialdehyde dehydrogenase and Organism(s) Haemophilus influenzae and UniProt Accession P44801
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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: Haemophilus influenzae
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 mechanism, role of substrate binding groups, residues Arg270, Glu243, Arg103, and Lys246 are involved
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L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH + H+
catalytic mechanism, function of the catalytic nucleophile Cys136 and the acid-base catalytic His277, the latter is also stabilizing the hemithioacetal intermediate
L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH + H+
catalytic mechanism, identification and structural characterization of the tetrahedral reaction intermediate, substrate binding structure
L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH + H+
catalytic mechanism, substrate recognition
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-4-aspartyl phosphate + NADPH
L-aspartate-4-semialdehyde + phosphate + NADP+
physiological forward reaction, reductive dephosphorylation in the aspartate biosynthetic pathway
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r
L-4-aspartyl phosphate + NADPH + H+
L-aspartate 4-semialdehyde + phosphate + NADP+
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-
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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 + cacodylate + NADP+
L-4-aspartyl cacodylate + NADPH
10% of the activity with phosphate
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r
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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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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oxyanion binding sites and structures with arsenate and periodate
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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
reductive dephosphorylation in the aspartate biosynthetic pathway
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r
L-aspartate-4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
formation of an acyl-enzyme intermediate
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r
L-aspartate-4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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reductive dephosphorylation in the aspartate biosynthetic pathway, aspartate-beta-semialdehydr is the key intermediate in biosynthesis of diaminopimelic acid
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r
L-aspartate-4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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formation of an acyl-enzyme intermediate
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r
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+
physiological forward reaction, reductive dephosphorylation in the aspartate biosynthetic pathway
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r
L-4-aspartyl phosphate + NADPH + H+
L-aspartate 4-semialdehyde + phosphate + NADP+
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-
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r
L-aspartate-4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
reductive dephosphorylation in the aspartate biosynthetic pathway
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-
r
L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde + phosphate + NADP+
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-
-
?
L-aspartate-4-semialdehyde + phosphate + NADP+
L-4-aspartyl phosphate + NADPH
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reductive dephosphorylation in the aspartate biosynthetic pathway, aspartate-beta-semialdehydr is the key intermediate in biosynthesis of diaminopimelic acid
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r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
S-methyl cysteine sulfoxide
inhibitor binding structure deduced from crystal structure
additional information
inhibitor binding structure and mechanism
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.2
L-aspartate-4-semialdehyde
recombinant wild-type enzyme, pH 9.0, 30°C
0.5
L-aspartate-4-semialdehyde
recombinant mutant H277N, pH 9.0, 30°C
0.1
L-aspartate-4-semialdehyde
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recombinant mutant R103K and mutant K246L
0.2
L-aspartate-4-semialdehyde
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recombinant wild-type enzyme and mutant E243D
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.2
L-aspartate-4-semialdehyde
recombinant mutant H277N, pH 9.0, 30°C
330
L-aspartate-4-semialdehyde
recombinant wild-type enzyme, pH 9.0, 30°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
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
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
10 mg/ml purified recombinant wild-type and mutant enzymes free or in complex with the substrates, protein in 10 mM HEPES, pH 7.0, 1 mM EDTA, 1 mM DTT, by hanging drop vapour diffusion, 20°C, mixed with equal volume of precipitant solution containing 22-24% PEG 3350, and 0.2 M ammonium acetate, crystals are soaked for 1 h in a solution containing 2 mM aspartate-beta-semialdehyde or 100 mM phosphate, 26% PEG 3350, 0.2 M ammonium acetate, 0.1 M Tris-HCl, pH 8.5, and 20% glycerol, X-ray diffraction structure determination and analysis at about 2.0 A resolution
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15 mg/ml purified recombinant enzyme, in 10 mM HEPES, pH 7.0, 1 mM EDTA, 1 mM DTT, crystallized as apoenzyme, as hemithioacetal, or as hemithioacetal structure with bound phosphate, hanging drop vapour diffusion method, 20°C, 1:1 mixture of protein solution and precipitant solution, the latter containing 24-28% PEG 3350, 0.2 M ammonium acetate, 0.1 M Tris, pH 8.5, overnight, substrate complexing by soaking of crystals in mother liquor with 50 mM potassium phosphate, crystals are frozen in precipitant solution with 20% glycerol added, X-ray diffraction structure determination and analysis at 2.0-2.15 A resolution, modeling
15 mg/ml purified recombinant wild-type enzyme in 10 mM HEPES, pH 7.0, 1 mM EDTA, and 1 mM DTT, enzyme is free or complexed with substrates phosphate and/or asparate-beta-semialdehyde, hanging drop vapour diffusion method, 20°C, against an equal volume of precipitant solution containing 24-28% PEG 3350, 0.2 M ammonium acetate, and 0.1 M Tris-HCl, pH 8.5, soaking of crystals before harvest in 100 mM phosphate and 2 mM aspartate-beta-semialdehyde, crystallization of mutant H277N in 10 mM HEPES, pH 7.0, 1 mM EDTA, and 1 mM DTT, by addition of precipitant solution containing 5 mM NADP+ and 5 mM inhibitor S-methyl-L-cysteine sulfoxide, 22% PEG 3350, 0.2 M ammonium acetate and 0.1 M sodium cacodylate, pH 6.5, X-ray diffraction structure determination and analysis at about 2.0 A resolution
about 10 mg/ml pure recombinant wild-type enzyme in 10 mM HEPES, pH 7.0, 1 mM EDTA, and 1 mM DTT, complexed with oxyanions arsenate or periodate, hanging drop vapour diffusion method, 20°C, against an equal volume of precipitant solution containing 22-24% PEG 4000, 0.2 M ammonium acetate, and Tris-HCl, pH 8.5, soaking of crystals before harvest in a solution containing 26% PEG3350, 0.2 M ammonium acetate, 100 mM periodate or arsenate,0.1 M Tris-HCl, pH 8.5, and 20% glycerol, X-ray diffraction structure determination and analysis at 2.3 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C136S
E243D
the mutant shows 1.2% activity compared to the wild type enzyme
H277N
K246R
the mutant shows 3.3% activity compared to the wild type enzyme
R103K
the mutant shows 0.4% activity compared to the wild type enzyme
R103L
the mutant shows 0.07% activity compared to the wild type enzyme
R267L
the mutant shows 9.5% activity compared to the wild type enzyme
R270K
the mutant shows 0.1% activity compared to the wild type enzyme
E243D
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site-directed mutagenesis, unaltered Km for the substrates but 8fold increased Km for cofactor NADP+, active site structural alterations
K246R
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site-directed mutagenesis, mutation of a putative phosphate binding residue, unaltered substrate Km, active site structural alterations
R103K
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site-directed mutagenesis, adversely affected interaction between enzyme and phosphate, active site structural alterations
R103L
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site-directed mutagenesis, altered interaction between enzyme and phosphate, active site structural alterations
R270K
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site-directed mutagenesis, active site mutant, unaltered substrate Km, active site structural alterations
C136S
site-directed mutagenesis, active site mutant is nearly inactive due to decrease in nuleophilicity, and also by a change in the orientation of the histidine imidazole ring
H277N
site-directed mutagenesis, active site mutant shows 100fold decreased catalytic efficiency compared to the wild-type enzyme, shift in the position of the bound reaction intermediate
H277N
the mutant shows 1% activity compared to the wild type enzyme
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
stability of recombinant wild-type and mutant enzymes, oveview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
using ammonium sulfate precipitation and column chromatography on Q Sepharose XL and Procion Red-A
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Moore, R.A.; Bocik, W.E.; Viola, R.E.
Expression and purification of aspartate beta-semialdehyde dehydrogenase from infectious microorganisms
Protein Expr. Purif.
25
189-194
2002
Haemophilus influenzae, Helicobacter pylori (O25801), Helicobacter pylori, Pseudomonas aeruginosa (Q51344), Pseudomonas aeruginosa, Vibrio cholerae (P23247), Vibrio cholerae
Blanco, J.; Moore, R.A.; Faehnle, C.R.; Coe, D.M.; Viola, R.E.
The role of substrate-binding groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase
Acta Crystallogr. Sect. D
60
1388-1395
2004
Haemophilus influenzae
Blanco, J.; Moore, R.A.; Faehnle, C.R.; Viola, R.E.
Critical catalytic functional groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase
Acta Crystallogr. Sect. D
60
1808-1815
2004
Haemophilus influenzae (P44801), Haemophilus influenzae
Faehnle, C.R.; Blanco, J.; Viola, R.E.
Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase
Acta Crystallogr. Sect. D
60
2320-2324
2004
Haemophilus influenzae (P44801)
Blanco, J.; Moore, R.A.; Viola, R.E.
Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase
Proc. Natl. Acad. Sci. USA
100
12613-12617
2003
no activity in Homo sapiens, Haemophilus influenzae (P44801), Haemophilus influenzae
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)
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