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Literature summary for 2.3.1.265 extracted from
- The molecular mechanism of substrate recognition and catalysis of the membrane acyltransferase PatA from Mycobacteria (2018), ACS Chem. Biol., 13, 131-140 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene MSMEG_2934, recombinant enzyme expression | Mycolicibacterium smegmatis |
| gene Rv2611c, the third gene of a cluster of five ORFs potentially organized as a single transcriptional unit and likely to be involved in the synthesis of PIMs | Mycobacterium tuberculosis |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| purified recombinant enzyme, cyrstallization attempts in the presence of Ac1PIM1/Ac2PIM1, Ac1PIM2/Ac2PIM2, or their deacylated analogues are unsuccessful. Crystallization of the enzyme in the presence of mannose phosphate, X-ray diffraction structure detremination and analysis at 2.42 A resolution, molecular replacement method and modelling | Mycolicibacterium smegmatis |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | inhibition mechanism analysis, overview | Mycobacterium tuberculosis |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| membrane | - |
Mycobacterium tuberculosis | 16020 | - |
| membrane | - |
Mycolicibacterium smegmatis | 16020 | - |
| additional information | the enzyme has a large negatively charged cytoplasmic part, overview | Mycobacterium tuberculosis | - |
- |
| additional information | the enzyme has a large negatively charged cytoplasmic part, overview | Mycolicibacterium smegmatis | - |
- |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycobacterium tuberculosis | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? |  |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycolicibacterium smegmatis | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycolicibacterium smegmatis ATCC 700084 | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycobacterium tuberculosis H37Rv | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycobacterium tuberculosis ATCC 25618 | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycolicibacterium smegmatis mc(2)155 | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycobacterium tuberculosis | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycolicibacterium smegmatis | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycolicibacterium smegmatis ATCC 700084 | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycobacterium tuberculosis H37Rv | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycobacterium tuberculosis ATCC 25618 | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | Mycolicibacterium smegmatis mc(2)155 | - |
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mycobacterium tuberculosis | P9WMB5 | - |
- |
| Mycobacterium tuberculosis ATCC 25618 | P9WMB5 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WMB5 | - |
- |
| Mycolicibacterium smegmatis | A0QWG5 | i.e. Mycobacterium smegmatis | - |
| Mycolicibacterium smegmatis ATCC 700084 | A0QWG5 | i.e. Mycobacterium smegmatis | - |
| Mycolicibacterium smegmatis mc(2)155 | A0QWG5 | i.e. Mycobacterium smegmatis | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant enzyme | Mycolicibacterium smegmatis |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | donor and acceptor binding sites and mechanism, catalytic mechanism, detailed overview | Mycolicibacterium smegmatis | ? | - |
- |
|
| additional information | donor and acceptor binding sites and mechanism, catalytic mechanism, detailed overview | Mycolicibacterium smegmatis ATCC 700084 | ? | - |
- |
|
| additional information | donor and acceptor binding sites and mechanism, catalytic mechanism, detailed overview | Mycolicibacterium smegmatis mc(2)155 | ? | - |
- |
|
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycobacterium tuberculosis | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycolicibacterium smegmatis | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycolicibacterium smegmatis ATCC 700084 | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycobacterium tuberculosis H37Rv | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycobacterium tuberculosis ATCC 25618 | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycolicibacterium smegmatis mc(2)155 | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycobacterium tuberculosis | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycolicibacterium smegmatis | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycolicibacterium smegmatis ATCC 700084 | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycobacterium tuberculosis H37Rv | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycobacterium tuberculosis ATCC 25618 | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
| palmitoyl-CoA + 2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol | - |
Mycolicibacterium smegmatis mc(2)155 | CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| membrane acyltransferase | - |
Mycobacterium tuberculosis |
| membrane acyltransferase | - |
Mycolicibacterium smegmatis |
| MSMEG_2934 | - |
Mycolicibacterium smegmatis |
| PatA | ambiguous | Mycobacterium tuberculosis |
| PatA | ambiguous | Mycolicibacterium smegmatis |
| phosphatidylinositol mannoside acyltransferase | UniProt | Mycobacterium tuberculosis |
| phosphatidylinositol mannoside acyltransferase | UniProt | Mycolicibacterium smegmatis |
| PIM acyltransferase | UniProt | Mycobacterium tuberculosis |
| PIM acyltransferase | UniProt | Mycolicibacterium smegmatis |
| Rv2611c | - |
Mycobacterium tuberculosis |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | the amino-acid sequences of Mycobacterium tuberculosis and Mycobacterium smegmatis versions of PIM acyltransferase display 74% sequence identity and 84% sequence similarity. All residues that participate in both of the catalytic and substrate recognition mechanisms are strictly conserved between both proteins | Mycobacterium tuberculosis |
| evolution | the amino-acid sequences of Mycobacterium tuberculosis and Mycobacterium smegmatis versions of PIM acyltransferase display 74% sequence identity and 84% sequence similarity. All residues that participate in both of the catalytic and substrate recognition mechanisms are strictly conserved between both proteins | Mycolicibacterium smegmatis |
| metabolism | the enzyme is part of the PIM biosynthetic pathway in mycobacteria, overview | Mycobacterium tuberculosis |
| metabolism | the enzyme is part of the PIM biosynthetic pathway in mycobacteria, overview | Mycolicibacterium smegmatis |
| additional information | the enzyme catalyzes the transfer of a palmitoyl moiety from palmitoyl-CoA to the 6-position of the mannose ring linked to the 2-position of inositol in PIM1/PIM2. The crystal structure of the enzyme in the presence of 6-O-palmitoyl-alpha-D-mannopyranoside unravels the acceptor binding mechanism. The acceptor mannose ring localizes in a cavity at the end of a surface-exposed long groove where the active site is located, whereas the palmitate moiety accommodates into a hydrophobic pocket deeply buried in the alpha/beta core of the protein. Both fatty acyl chains of the PIM2 acceptor are essential for the reaction to take place, highlighting their critical role in the generation of a competent active site. By the use of combined structural and quantummechanics/molecular-mechanics (QM/MM) meta-dynamics, the catalytic mechanism of PatA is described at the atomic-electronic level, detailed structural rationale for a stepwise reaction, with the generation of a tetrahedral transition state for the rate-determining step, glycolipid acceptor binding site and the catalytic mechanism of PatA, overview | Mycobacterium tuberculosis |
| additional information | the enzyme catalyzes the transfer of a palmitoyl moiety from palmitoyl-CoA to the 6-position of the mannose ring linked to the 2-position of inositol in PIM1/PIM2. The crystal structure of the enzyme in the presence of 6-O-palmitoyl-alpha-D-mannopyranoside unravels the acceptor binding mechanism. The acceptor mannose ring localizes in a cavity at the end of a surface-exposed long groove where the active site is located, whereas the palmitate moiety accommodates into a hydrophobic pocket deeply buried in the alpha/beta core of the protein. Both fatty acyl chains of the PIM2 acceptor are essential for the reaction to take place, highlighting their critical role in the generation of a competent active site. By the use of combined structural and quantummechanics/molecular-mechanics (QM/MM) meta-dynamics, the catalytic mechanism of PatA is described at the atomic-electronic level, detailed structural rationale for a stepwise reaction, with the generation of a tetrahedral transition state for the rate-determining step, glycolipid acceptor binding site and the catalytic mechanism of PatA, structure homology modeling, overview | Mycolicibacterium smegmatis |
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