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 (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 (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, 20°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 | Comment | Organism |
---|---|---|
C366S | mutant enzyme crystal structure analysis | Brucella suis bv. 1 |
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 | 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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Brucella suis bv. 1 | Q8G2R2 | - |
- |
Brucella suis bv. 1 1330 | Q8G2R2 | - |
- |
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 | 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 | Comment | Organism |
---|---|---|
homodimer | - |
Brucella suis bv. 1 |
More | quaternary structure of enzyme BsHDH, overview | Brucella suis bv. 1 |
Synonyms | Comment | Organism |
---|---|---|
BsHDH | - |
Brucella suis bv. 1 |
L-histidinol dehydrogenase | - |
Brucella suis bv. 1 |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Brucella suis bv. 1 |
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 |