Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a potential target for development of therapeutic agents against visceral leishmaniasis | Leishmania donovani |
drug development | the enzyme is a potential target for drug development | Leishmania donovani |
Cloned (Comment) | Organism |
---|---|
DNA and amino acid sequence determination and analysis, overexpression of the His-tagged NMT in Escherichia coli strain BL21(DE3) pRareS | Leishmania donovani |
overexpression in Escherichia coli strain BL21(DE3) | Leishmania donovani |
Crystallization (Comment) | Organism |
---|---|
purified recombinant enzyme in complex with the non-hydrolysable substrate analogue S-(2-oxo)pentadecyl-CoA, X-ray diffraction structure determination and analysis at 1.4 A resolution, molecular replacement method | Leishmania donovani |
purified recombinant His-tagged NMT in complex with the non-hydrolysable substrate analogue S-(2-oxo)pentadecyl-CoA, hanging drop vapour diffusion method, mixing of 0.00125 ml of protein solution containing 8 mg/ml protein in 50 mM Tris, pH 8.0, 50 mM NaCl , with 0.00125 l of reservoir solution containing 0.6 M lithium chloride, 20% w/v PEG 6000, 4% v/v 1,4-butanediol in 0.5 M sodium citrate, pH 4.0, equilibration against 0.8 ml of reservoir solution, 20°C, X-ray diffraction structure determination and analysis at 1.4 A resolution, molecular replacement | Leishmania donovani |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | ligand binding structure-function analysis for drug design, overview | Leishmania donovani | |
S-(2-oxo)pentadecyl-CoA | i.e. NHM, a non-hydrolysable myristoyl-CoA analogue, binding structure analysis, overview; i.e. NHM, a non-hydrolysable myristoyl-CoA analogue, binding structure, overview | Leishmania donovani |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00023 | - |
myristoyl-CoA | pH 7.4, 37°C, recombinant enzyme | Leishmania donovani | |
0.0175 | - |
ARF peptide | pH 7.4, 37°C, recombinant enzyme | Leishmania donovani |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Leishmania donovani |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
tetradecanoyl-CoA + glycylpeptide | Leishmania donovani | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction | CoA + N-tetradecanoylglycylpeptide | - |
? | |
tetradecanoyl-CoA + glycylpeptide | Leishmania donovani LV9 | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction | CoA + N-tetradecanoylglycylpeptide | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Leishmania donovani | D0AB09 | - |
- |
Leishmania donovani LV9 | D0AB09 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant enzyme from Escherichia coli strain BL21(DE3) | Leishmania donovani |
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) pRareS by metal affinity chromatography and gel filtration, removal of the His-tag by cleavage with HRV 3C protease | Leishmania donovani |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
promastigote | - |
Leishmania donovani | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | the fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the carboxy-terminal lobe, substrate binding structure, overview | Leishmania donovani | ? | - |
? | |
additional information | the fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the carboxy-terminal lobe, substrate binding structure, overview | Leishmania donovani LV9 | ? | - |
? | |
myristoyl-CoA + ARF peptide | C-terminally biotinylated ARF peptide, i.e. GLYVSRLFNRLFQKK(Biotin)-NH2, substrate binding structures, overview | Leishmania donovani | CoA + N-myristoyl-ARF peptide | - |
? | |
tetradecanoyl-CoA + GAAPSKIV-NH2 | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a protein. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the C-terminal lobe, substrate binding structure, overview | Leishmania donovani | CoA + N-tetradecanoyl-GAAPSKIV-NH2 | - |
? | |
tetradecanoyl-CoA + GAAPSKIV-NH2 | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a protein. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the C-terminal lobe, substrate binding structure, overview | Leishmania donovani LV9 | CoA + N-tetradecanoyl-GAAPSKIV-NH2 | - |
? | |
tetradecanoyl-CoA + GLTISKLFRR | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a protein. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the C-terminal lobe, substrate binding structure, overview | Leishmania donovani | CoA + N-tetradecanoyl-GLTISKLFRR | - |
? | |
tetradecanoyl-CoA + GLTISKLFRR | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a protein. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the C-terminal lobe, substrate binding structure, overview | Leishmania donovani LV9 | CoA + N-tetradecanoyl-GLTISKLFRR | - |
? | |
tetradecanoyl-CoA + glycylpeptide | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction | Leishmania donovani | CoA + N-tetradecanoylglycylpeptide | - |
? | |
tetradecanoyl-CoA + glycylpeptide | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction | Leishmania donovani LV9 | CoA + N-tetradecanoylglycylpeptide | - |
? | |
tetradecanoyl-CoA + GLYVSRLFNRLFQKK(biotin) | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a protein. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the C-terminal lobe, substrate binding structure, overview | Leishmania donovani | CoA + N-tetradecanoyl-GLYVSRLFNRLFQKK(biotin) | - |
? | |
tetradecanoyl-CoA + GLYVSRLFNRLFQKK(biotin) | NMT catalyses the attachment of the 14C saturated fatty acid, myristate, to the N-terminal glycine residue of a protein. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the C-terminal lobe, substrate binding structure, overview | Leishmania donovani LV9 | CoA + N-tetradecanoyl-GLYVSRLFNRLFQKK(biotin) | - |
? |
Synonyms | Comment | Organism |
---|---|---|
myristoyl-CoA-protein N-myristoyltransferase | - |
Leishmania donovani |
N-myristoyltransferase | - |
Leishmania donovani |
NMT | - |
Leishmania donovani |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Leishmania donovani |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Leishmania donovani |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000687 | - |
- |
Leishmania donovani | S-(2-oxo)pentadecyl-CoA | |
0.0687 | - |
pH 7.4, 37°C, recombinant enzyme | Leishmania donovani | S-(2-oxo)pentadecyl-CoA |
General Information | Comment | Organism |
---|---|---|
physiological function | NMT function is essential for viability in host cells and in insect stages of the pathogenic protozoan parasite | Leishmania donovani |
physiological function | NMT catalyses the attachment of the 14-carbon saturated fatty acid, myristate, to the amino-terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction. In these pathways, N-myristoylation facilitates association of substrate proteins with membranes or the hydrophobic domains of other partner peptides. NMT function is essential for viability in all cell types tested to date | Leishmania donovani |