Cloned (Comment) | Organism |
---|---|
expression in Escherichia coli | Aquifex aeolicus |
Protein Variants | Comment | Organism |
---|---|---|
E126A | site-directed mutagenesis, the mutant is almost inactive, formation of an organometallic species with HMBPP, a pi/sigma metallacycle or nu2-alkenyl complex, overview | Aquifex aeolicus |
H124A | site-directed mutagenesis, the mutant shows an increased Km and a 5fold decreased Vmax compared to the wild-type enzyme | Aquifex aeolicus |
H42A | site-directed mutagenesis, the mutant shows a decreased Vmax but unaltered Km compared to the wild-type enzyme | Aquifex aeolicus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | alkyne diphosphates are potent IspH inhibitors that form metallacycle complexes. Identification of inhibitors using the metallacycle model | Aquifex aeolicus | |
propargyl alcohol | weak inhibition, binding structure, overview | Aquifex aeolicus | |
propargyl diphosphate | binding structure, overview | Aquifex aeolicus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
(E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H + H+ | Aquifex aeolicus | HMBPP reductase catalyzes the 2H+/2e- reduction of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate to form an approximately 5:1 mixture of isopentenyl diphosphate and dimethylallyl diphosphate, insights into IspH catalysis and inhibition, involving organometallic species. Residue E126 is essential for catalytic activity. Residue H124 is not a major contributor to substrate binding, but is essential for catalysis, it is involved in delivering H+ to E126 and the bound (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate. Residue H42 forms hydrogen bonds to the bound diphosphate ligand. Ligand binding structure spectral analysis and modelling, overview | dimethylallyl diphosphate + NAD(P)+ + H2O | - |
r | |
(E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H + H+ | Aquifex aeolicus | HMBPP reductase catalyzes the 2H+/2e- reduction of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate to form an approximately 5:1 mixture of isopentenyl diphosphate and dimethylallyl diphosphate, insights into IspH catalysis and inhibition, involving organometallic species. Residue E126 is essential for catalytic activity. Residue H124 is not a major contributor to substrate binding, but is essential for catalysis, it is involved in delivering H+ to E126 and the bound (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate. Residue H42 forms hydrogen bonds to the bound diphosphate ligand. Ligand binding structure spectral analysis and modelling, overview | isopentenyl diphosphate + NAD(P)+ + H2O | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Aquifex aeolicus | - |
gene lytB | - |
no activity in Homo sapiens | - |
- |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
dimethylallyl diphosphate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ | reaction mechanism, role of protein residues in the IspH mechanism, detailed overview | Aquifex aeolicus | |
isopentenyl diphosphate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ | reaction mechanism, role of protein residues in the IspH mechanism, detailed overview | Aquifex aeolicus |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
(E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H + H+ | HMBPP reductase catalyzes the 2H+/2e- reduction of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate to form an approximately 5:1 mixture of isopentenyl diphosphate and dimethylallyl diphosphate, insights into IspH catalysis and inhibition, involving organometallic species. Residue E126 is essential for catalytic activity. Residue H124 is not a major contributor to substrate binding, but is essential for catalysis, it is involved in delivering H+ to E126 and the bound (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate. Residue H42 forms hydrogen bonds to the bound diphosphate ligand. Ligand binding structure spectral analysis and modelling, overview | Aquifex aeolicus | dimethylallyl diphosphate + NAD(P)+ + H2O | - |
r | |
(E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H + H+ | HMBPP reductase catalyzes the 2H+/2e- reduction of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate to form an approximately 5:1 mixture of isopentenyl diphosphate and dimethylallyl diphosphate, insights into IspH catalysis and inhibition, involving organometallic species. Residue E126 is essential for catalytic activity. Residue H124 is not a major contributor to substrate binding, but is essential for catalysis, it is involved in delivering H+ to E126 and the bound (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate. Residue H42 forms hydrogen bonds to the bound diphosphate ligand. Ligand binding structure spectral analysis and modelling, overview | Aquifex aeolicus | isopentenyl diphosphate + NAD(P)+ + H2O | - |
r |
Synonyms | Comment | Organism |
---|---|---|
E-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase | - |
Aquifex aeolicus |
HMBPP reductase | - |
Aquifex aeolicus |
ispH | - |
Aquifex aeolicus |
LytB | - |
Aquifex aeolicus |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.97 | - |
propargyl diphosphate | pH not specified in the publication, temperature not specified in the publication | Aquifex aeolicus | |
10 | - |
propargyl alcohol | above, pH not specified in the publication, temperature not specified in the publication | Aquifex aeolicus |
General Information | Comment | Organism |
---|---|---|
physiological function | the enzyme is essential for survival | Aquifex aeolicus |