Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-methoxyphenyl)methylidene]propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-methylphenyl)methylidene]propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-nitrophenyl)methylidene]propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-phenoxyphenyl)methylidene]propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(naphthalen-2-yl)methylidene]propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-phenylmethylidene]propanehydrazide (non-preferred name) | - |
Mycobacterium tuberculosis | |
2-amino-N'-[(E)-(2-hydroxyphenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-N'-[(E)-(4-bromophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-N'-[(E)-(4-chlorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-N'-[(E)-(4-fluorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | - |
Mycobacterium tuberculosis | |
2-amino-N'-[(E)-[4-(dimethylamino)phenyl]methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | - |
Mycobacterium tuberculosis | |
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] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
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 | |
0.0027 | - |
NAD+ | pH 7.2, 25°C, with Ficoll at 100 g/l | Mycobacterium tuberculosis | |
0.0029 | - |
NAD+ | pH 7.2, 25°C | Mycobacterium tuberculosis | |
0.0033 | - |
NAD+ | pH 7.2, 25°C, with Ficoll at 200 g/l | Mycobacterium tuberculosis | |
0.017 | - |
L-histidinol | pH 7.2, 25°C, with Ficoll at 100 g/l | Mycobacterium tuberculosis | |
0.02 | - |
L-histidinol | pH 7.2, 25°C | Mycobacterium tuberculosis | |
0.022 | - |
L-histidinol | pH 7.2, 25°C, with Ficoll at 200 g/l | Mycobacterium tuberculosis |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | dependent on | Mycobacterium tuberculosis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-histidinol + 2 NAD+ + H2O | Mycobacterium tuberculosis | - |
L-histidine + 2 NADH + 3 H+ | - |
? | |
L-histidinol + 2 NAD+ + H2O | Mycobacterium tuberculosis H37Rv | - |
L-histidine + 2 NADH + 3 H+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacterium tuberculosis | P9WNW9 | - |
- |
Mycobacterium tuberculosis H37Rv | P9WNW9 | - |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
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 |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-histidinol + 2 NAD+ + H2O | - |
Mycobacterium tuberculosis | L-histidine + 2 NADH + 3 H+ | - |
? | |
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+ | - |
? | |
L-histidinol + 2 NAD+ + H2O | - |
Mycobacterium tuberculosis H37Rv | L-histidine + 2 NADH + 3 H+ | - |
? | |
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+ | - |
? | |
additional information | imidazole-containing substrate analogues are likely to bind to free enzyme | Mycobacterium tuberculosis | ? | - |
? | |
additional information | imidazole-containing substrate analogues are likely to bind to free enzyme | Mycobacterium tuberculosis H37Rv | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
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 | Comment | Organism |
---|---|---|
HDH | - |
Mycobacterium tuberculosis |
HisD | - |
Mycobacterium tuberculosis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
15 | 40 | assay at | Mycobacterium tuberculosis |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.227 | - |
NAD+ | pH 7.2, 25°C, with Ficoll at 200 g/l | Mycobacterium tuberculosis | |
1.134 | - |
NAD+ | pH 7.2, 25°C, with Ficoll at 100 g/l | Mycobacterium tuberculosis | |
1.209 | - |
L-histidinol | pH 7.2, 25°C, with Ficoll at 100-200 g/l | Mycobacterium tuberculosis | |
1.361 | - |
NAD+ | pH 7.2, 25°C | Mycobacterium tuberculosis | |
1.436 | - |
L-histidinol | pH 7.2, 25°C | Mycobacterium tuberculosis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.2 | 9 | assay at | Mycobacterium tuberculosis |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Mycobacterium tuberculosis |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | inhibition kinetics of hydrozone derivative inhibitors with enzyme MtHisD | Mycobacterium tuberculosis | |
0.00047 | - |
2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(naphthalen-2-yl)methylidene]propanehydrazide | pH 7.2, 25°C | Mycobacterium tuberculosis | |
0.00064 | - |
2-amino-N'-[(E)-(4-chlorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | pH 7.2, 25°C | Mycobacterium tuberculosis | |
0.0032 | - |
2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-phenoxyphenyl)methylidene]propanehydrazide | pH 7.2, 25°C | Mycobacterium tuberculosis | |
0.013 | - |
2-amino-N'-[(E)-(4-fluorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | pH 7.2, 25°C | Mycobacterium tuberculosis |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0011 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(naphthalen-2-yl)methylidene]propanehydrazide | |
0.0024 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-N'-[(E)-(4-chlorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | |
0.0024 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-N'-[(E)-(4-fluorophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | |
0.0025 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-nitrophenyl)methylidene]propanehydrazide | |
0.005 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-methoxyphenyl)methylidene]propanehydrazide | |
0.0055 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-methylphenyl)methylidene]propanehydrazide | |
0.0077 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-N'-[(E)-(4-bromophenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | |
0.0091 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-N'-[(E)-[4-(dimethylamino)phenyl]methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | |
0.0098 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-3-(1H-imidazol-4-yl)-N'-[(E)-(4-phenoxyphenyl)methylidene]propanehydrazide | |
0.027 | - |
pH 7.2, 25°C | Mycobacterium tuberculosis | 2-amino-N'-[(E)-(2-hydroxyphenyl)methylidene]-3-(1H-imidazol-4-yl)propanehydrazide | |
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 | Comment | Organism |
---|---|---|
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 |
physiological function | the enzyme is essential for Mycobacterium tuberculosis survival in vitro | Mycobacterium tuberculosis |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
68.78 | - |
NAD+ | pH 7.2, 25°C, with Ficoll at 200 g/l | Mycobacterium tuberculosis | |
420 | - |
NAD+ | pH 7.2, 25°C, with Ficoll at 100 g/l | Mycobacterium tuberculosis | |
469 | - |
NAD+ | pH 7.2, 25°C | Mycobacterium tuberculosis | |
54950 | - |
L-histidinol | pH 7.2, 25°C, with Ficoll at 200 g/l | Mycobacterium tuberculosis | |
71120 | - |
L-histidinol | pH 7.2, 25°C, with Ficoll at 100 g/l | Mycobacterium tuberculosis | |
71800 | - |
L-histidinol | pH 7.2, 25°C | Mycobacterium tuberculosis |