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Literature summary extracted from

  • Lunardi, J.; Borges Martinelli, L.; Raupp, A.; Sacconi Nunes, J.; Rostirolla, D.; Saraiva Macdo Timmers, L.; Villela, A.; Pissinate, K.; Limberger, J.; Norberto De Souza, O.; Basso, L.; Santos, D.; Machado, P.
    Mycobacterium tuberculosis histidinol dehydrogenase: Biochemical characterization and inhibition studies (2016), RSC Adv., 6, 28406-28418.
No PubMed abstract available

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.23 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-methoxyphenyl)methylidene]propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-methylphenyl)methylidene]propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-nitrophenyl)methylidene]propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-phenoxyphenyl)methylidene]propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(naphthalen-2-yl)methylidene]propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-phenylmethylidene]propanehydrazide (non-preferred name)
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-N'-[(E)-(2-hydroxyphenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-N'-[(E)-(4-bromophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-N'-[(E)-(4-chlorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-N'-[(E)-(4-fluorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 2-amino-N'-[(E)-[4-(dimethylamino)phenyl]methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
-
 Mycobacterium tuberculosis
1.1.1.23 additional information synthesis of hydrazones derived from L-histidine as enzyme inhibitors in the low micromolar range, overview. Molecular docking study and enzyme-inhibitor complex structure analysis Mycobacterium tuberculosis

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.23 additional information
-
 additional information pre-steady-state kinetics and Michaelis-Menten steady-state kinetics, solvent kinetic isotope effects and proton inventory, thermodynamics, detailed overview Mycobacterium tuberculosis
1.1.1.23 0.0027
-
 NAD+ pH 7.2, 25°C, with Ficoll at 100 g/l Mycobacterium tuberculosis
1.1.1.23 0.0029
-
 NAD+ pH 7.2, 25°C Mycobacterium tuberculosis
1.1.1.23 0.0033
-
 NAD+ pH 7.2, 25°C, with Ficoll at 200 g/l Mycobacterium tuberculosis
1.1.1.23 0.017
-
 L-histidinol pH 7.2, 25°C, with Ficoll at 100 g/l Mycobacterium tuberculosis
1.1.1.23 0.02
-
 L-histidinol pH 7.2, 25°C Mycobacterium tuberculosis
1.1.1.23 0.022
-
 L-histidinol pH 7.2, 25°C, with Ficoll at 200 g/l Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.1.1.23 Zn2+ dependent on Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.23 L-histidinol + 2 NAD+ + H2O Mycobacterium tuberculosis
-
 L-histidine + 2 NADH + 3 H+
-
 ?
1.1.1.23 L-histidinol + 2 NAD+ + H2O Mycobacterium tuberculosis H37Rv
-
 L-histidine + 2 NADH + 3 H+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.23 Mycobacterium tuberculosis P9WNW9
-
-
1.1.1.23 Mycobacterium tuberculosis H37Rv P9WNW9
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.1.1.23 L-histidinol + 2 NAD+ + H2O = L-histidine + 2 NADH + 2 H+ enzyme HisD from Mycobacterium tuberculosis follows a bi uni uni bi ping-pong mechanism in which L-histidinol is the first substrate to bind and L-histidine the last product to dissociate, the amino acid side chains of His336 and Glu335 are likely involved in catalysis and/or substrate binding Mycobacterium tuberculosis
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.23 L-histidinol + 2 NAD+ + H2O
-
 Mycobacterium tuberculosis L-histidine + 2 NADH + 3 H+
-
 ?
1.1.1.23 L-histidinol + 2 NAD+ + H2O NAD+- and Zn+-dependent conversion of L-histidinol to L-histidine through an L-histidinaldehyde intermediate, leading to the concomitant reduction of 2 NAD+ molecules Mycobacterium tuberculosis L-histidine + 2 NADH + 3 H+
-
 ?
1.1.1.23 L-histidinol + 2 NAD+ + H2O
-
 Mycobacterium tuberculosis H37Rv L-histidine + 2 NADH + 3 H+
-
 ?
1.1.1.23 L-histidinol + 2 NAD+ + H2O NAD+- and Zn+-dependent conversion of L-histidinol to L-histidine through an L-histidinaldehyde intermediate, leading to the concomitant reduction of 2 NAD+ molecules Mycobacterium tuberculosis H37Rv L-histidine + 2 NADH + 3 H+
-
 ?
1.1.1.23 additional information imidazole-containing substrate analogues are likely to bind to free enzyme Mycobacterium tuberculosis ?
-
 ?
1.1.1.23 additional information imidazole-containing substrate analogues are likely to bind to free enzyme Mycobacterium tuberculosis H37Rv ?
-
 ?

Subunits

EC Number Subunits Comment Organism
1.1.1.23 homodimer the monomers, subunits A and B, possess four globular domains. The two active sites are located at the boundary of the homodimer interface. Domains 1, 2, and 4 are related to L-histidinol and Zn2+ binding, and domain 1 to NAD+ molecule binding Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
1.1.1.23 HDH
-
 Mycobacterium tuberculosis
1.1.1.23 HisD
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.1.1.23 15 40 assay at Mycobacterium tuberculosis

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.1.1.23 0.227
-
 NAD+ pH 7.2, 25°C, with Ficoll at 200 g/l Mycobacterium tuberculosis
1.1.1.23 1.134
-
 NAD+ pH 7.2, 25°C, with Ficoll at 100 g/l Mycobacterium tuberculosis
1.1.1.23 1.209
-
 L-histidinol pH 7.2, 25°C, with Ficoll at 100-200 g/l Mycobacterium tuberculosis
1.1.1.23 1.361
-
 NAD+ pH 7.2, 25°C Mycobacterium tuberculosis
1.1.1.23 1.436
-
 L-histidinol pH 7.2, 25°C Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.1.1.23 7.2 9 assay at Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.23 NAD+
-
 Mycobacterium tuberculosis

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.1.1.23 additional information
-
 additional information inhibition kinetics of hydrozone derivative inhibitors with enzyme MtHisD Mycobacterium tuberculosis
1.1.1.23 0.00047
-
 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(naphthalen-2-yl)methylidene]propanehydrazide pH 7.2, 25°C Mycobacterium tuberculosis
1.1.1.23 0.00064
-
 2-amino-N'-[(E)-(4-chlorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide pH 7.2, 25°C Mycobacterium tuberculosis
1.1.1.23 0.0032
-
 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-phenoxyphenyl)methylidene]propanehydrazide pH 7.2, 25°C Mycobacterium tuberculosis
1.1.1.23 0.013
-
 2-amino-N'-[(E)-(4-fluorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide pH 7.2, 25°C Mycobacterium tuberculosis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.1.1.23 0.0011
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(naphthalen-2-yl)methylidene]propanehydrazide
1.1.1.23 0.0024
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-N'-[(E)-(4-chlorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
1.1.1.23 0.0024
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-N'-[(E)-(4-fluorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
1.1.1.23 0.0025
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-nitrophenyl)methylidene]propanehydrazide
1.1.1.23 0.005
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-methoxyphenyl)methylidene]propanehydrazide
1.1.1.23 0.0055
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-methylphenyl)methylidene]propanehydrazide
1.1.1.23 0.0077
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-N'-[(E)-(4-bromophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
1.1.1.23 0.0091
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-N'-[(E)-[4-(dimethylamino)phenyl]methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
1.1.1.23 0.0098
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-phenoxyphenyl)methylidene]propanehydrazide
1.1.1.23 0.027
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-N'-[(E)-(2-hydroxyphenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide
1.1.1.23 0.029
-
 pH 7.2, 25°C Mycobacterium tuberculosis 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-phenylmethylidene]propanehydrazide (non-preferred name)

General Information

EC Number General Information Comment Organism
1.1.1.23 additional information MtHisD is a bifunctional four-electron dehydrogenase enzyme that catalyzes two subsequent reactions, the oxidation of L-Hol and the reduction of two NAD+ molecules,23 with the formation of two intermediaries, L-histidinaldehyde and L-histidindiol. L-histidinaldehyde is very unstable at neutral pH when not bound to HisD Mycobacterium tuberculosis
1.1.1.23 physiological function the enzyme is essential for Mycobacterium tuberculosis survival in vitro Mycobacterium tuberculosis

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
1.1.1.23 68.78
-
 NAD+ pH 7.2, 25°C, with Ficoll at 200 g/l Mycobacterium tuberculosis
1.1.1.23 420
-
 NAD+ pH 7.2, 25°C, with Ficoll at 100 g/l Mycobacterium tuberculosis
1.1.1.23 469
-
 NAD+ pH 7.2, 25°C Mycobacterium tuberculosis
1.1.1.23 54950
-
 L-histidinol pH 7.2, 25°C, with Ficoll at 200 g/l Mycobacterium tuberculosis
1.1.1.23 71120
-
 L-histidinol pH 7.2, 25°C, with Ficoll at 100 g/l Mycobacterium tuberculosis
1.1.1.23 71800
-
 L-histidinol pH 7.2, 25°C Mycobacterium tuberculosis