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Literature summary for 1.1.1.23 extracted from

  • D'Ambrosio, K.; Lopez, M.; Dathan, N.A.; Ouahrani-Bettache, S.; Koehler, S.; Ascione, G.; Monti, S.M.; Winum, J.Y.; De Simone, G.
    Structural basis for the rational design of new anti-Brucella agents: the crystal structure of the C366S mutant of L-histidinol dehydrogenase from Brucella suis (2014), Biochimie, 97, 114-120.
    View publication on PubMed

Application

Application Comment Organism
drug development L-histidinol dehydrogenase from Brucella suis is an enzyme involved in the histidine biosynthesis pathway which is absent in mammals, thus representing a very interesting target for the development of anti-Brucella agents Brucella suis bv. 1

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of GST-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)pLysS, recombinant expressiom of His6-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS Brucella suis bv. 1

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant detagged enzyme mutant C366S, in apoform or bound to inhibitor (3S)-3-amino-1-[4-(benzyloxy)phenyl]-4-(1H-imidazol-4-yl)butan-2-one, hanging drop vapor diffusion method, protein solution containing 50 mM Tris-HCl, 150 mM NaCl, and 1 mM DTT, as well as 1 mM ZnCl2 and 20 mM inhibitor 1, is mixed with reservoir solution containing 25% PEG 3350, 0.1 M HEPES pH 8, 0.25 M NaCl, 20Ā°C, equilibration against 1 ml of reservoir solution, method optimzation, X-ray diffraction structure determination and analysis at 1.90 A resolution, molecular replacement and modelling Brucella suis bv. 1

Protein Variants

Protein Variants Comment Organism
C366S mutant enzyme crystal structure analysis Brucella suis bv. 1

Inhibitors

Inhibitors Comment Organism Structure
(3S)-3-amino-1-[4-(benzyloxy)phenyl]-4-(1H-imidazol-4-yl)butan-2-one a nanomolar inhibitor, binding structure, overview Brucella suis bv. 1

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ required, active site-bound, one Zn2+ ion per monomer. The Zn2+ ion plays a crucial role in the proper positioning of the substrate, binding structure, overview Brucella suis bv. 1

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-histidinol + 2 NAD+ + H2O Brucella suis bv. 1
-
L-histidine + 2 NADH + 3 H+
-
?
L-histidinol + 2 NAD+ + H2O Brucella suis bv. 1 1330
-
L-histidine + 2 NADH + 3 H+
-
?

Organism

Organism UniProt Comment Textmining
Brucella suis bv. 1 Q8G2R2
-
-
Brucella suis bv. 1 1330 Q8G2R2
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant GST-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3)pLysS by glutathione affinity chromatography, tag cleavage, and gel filtration, and recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3)pLysS by nickel affinity chromatography and gel filtration Brucella suis bv. 1

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-histidinol + 2 NAD+ + H2O
-
Brucella suis bv. 1 L-histidine + 2 NADH + 3 H+
-
?
L-histidinol + 2 NAD+ + H2O two steps: NAD+-dependent oxidations of L-histidinol to L-histidinaldehyde and subsequently to L-histidine Brucella suis bv. 1 L-histidine + 2 NADH + 3 H+
-
?
L-histidinol + 2 NAD+ + H2O
-
Brucella suis bv. 1 1330 L-histidine + 2 NADH + 3 H+
-
?
L-histidinol + 2 NAD+ + H2O two steps: NAD+-dependent oxidations of L-histidinol to L-histidinaldehyde and subsequently to L-histidine Brucella suis bv. 1 1330 L-histidine + 2 NADH + 3 H+
-
?

Subunits

Subunits Comment Organism
homodimer
-
Brucella suis bv. 1
More quaternary structure of enzyme BsHDH, overview Brucella suis bv. 1

Synonyms

Synonyms Comment Organism
BsHDH
-
Brucella suis bv. 1
L-histidinol dehydrogenase
-
Brucella suis bv. 1

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Brucella suis bv. 1

General Information

General Information Comment Organism
metabolism the enzyme is involved in the histidine biosynthesis pathway catalyzing catalyzes the last two steps in the histidine biosynthesis pathway, namely the sequential NAD+-dependent oxidations of L-histidinol to L-histidinaldehyde and subsequently to L-histidine Brucella suis bv. 1
additional information residues Glu326 and His327 are directly involved in catalysis, the first participating in acid-base catalysis and the second activating a water molecule, active site structure, overview Brucella suis bv. 1