Literature summary for 2.3.1.265 extracted from

  • Tersa, M.; Raich, L.; Albesa-Jove, D.; Trastoy, B.; Prandi, J.; Gilleron, M.; Rovira, C.; Guerin, M.E.
    The molecular mechanism of substrate recognition and catalysis of the membrane acyltransferase PatA from Mycobacteria (2018), ACS Chem. Biol., 13, 131-140 .
    View publication on PubMed

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
-
-
membrane
-
Mycolicibacterium smegmatis
-
-
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-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 + 2,6-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-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 + 2,6-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-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 + 2,6-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-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 + 2,6-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 Mycolicibacterium smegmatis mc(2)155
-
CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol
-
?

Organism

Organism UniProt Comment Textmining
Mycolicibacterium smegmatis A0QWG5 i.e. Mycobacterium smegmatis
-
Mycobacterium tuberculosis P9WMB5
-
-
Mycolicibacterium smegmatis ATCC 700084 A0QWG5 i.e. Mycobacterium smegmatis
-
Mycobacterium tuberculosis H37Rv P9WMB5
-
-
Mycobacterium tuberculosis ATCC 25618 P9WMB5
-
-
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
PatA ambiguous Mycobacterium tuberculosis
PatA ambiguous Mycolicibacterium smegmatis
Rv2611c
-
Mycobacterium tuberculosis
membrane acyltransferase
-
Mycobacterium tuberculosis
membrane acyltransferase
-
Mycolicibacterium smegmatis
PIM acyltransferase UniProt Mycobacterium tuberculosis
PIM acyltransferase UniProt Mycolicibacterium smegmatis
phosphatidylinositol mannoside acyltransferase UniProt Mycobacterium tuberculosis
phosphatidylinositol mannoside acyltransferase UniProt Mycolicibacterium smegmatis
MSMEG_2934
-
Mycolicibacterium smegmatis

General Information

General Information Comment Organism
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
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
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