EC Number   |
General Information |
Reference |
|---|
   2.3.1.265 | 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 |
-, 755684 |
| 2.3.1.265 | malfunction |
disruption of gene MSMEG_2934 severely affects the groth of Mycobacterium smegmatis |
-, 756084 |
| 2.3.1.265 | malfunction |
disruption of gene Rv2611c abolishes the growth of Mycobacterium tuberculosis |
-, 756084 |
| 2.3.1.265 | metabolism |
the enzyme is part of the PIM biosynthetic pathway in mycobacteria, detailed overview. Ac1PIM6 and Ac2PIM6 seems to be located in the outer leaflet of the inner membrane. Palmitic acid (C16:0) and 10-methyloctadecanoic acid (i.e. tuberculostearic acid) are the major fatty acid constituents of the biochemically isolated inner membrane. PIM2 is composed of two mannose (Man) residues attached to positions 2 and 6 of the myo-inositol ring of phosphatidyl-1D-myo-inositol (PI), whereas PIM6 is composed of a pentamannosyl group, t-alpha-Man(1->2)-alpha-Man(1->2)-alpha-Man(1->6)-alpha-Man(1->6)-alpha-Man(1->, attached to position 6 of the myo-inositol ring), in addition to the Manp residue present at position 2. The triacylated forms of PIM2 and PIM6 (Ac1PIM2 and Ac1PIM6) show major acyl forms containing two palmitic acid residues (C16) and one tuberculostearic acid residue (10-methyloctadecanoate, C19), where one fatty acyl chain is linked to the Manp residue attached to position 2 of myo-inositol, and two fatty acyl chains are located on the glycerol moiety. The tetraacylated forms, Ac2PIM2 and Ac2PIM6, are present predominantly as two populations bearing either three C16/one C19 or two C16/two C19. Two fatty acyl chains are located on the glycerol moiety, one fatty acyl chain is linked to the Manp residue attached to position 2 of myo-inositol and one fatty acyl chain is attached to position 3 of the myo-inositol unit |
-, 756084 |
| 2.3.1.265 | metabolism |
the enzyme is part of the PIM biosynthetic pathway in mycobacteria, overview |
-, 755684 |
| 2.3.1.265 | more |
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 |
-, 755684 |
| 2.3.1.265 | physiological function |
the PIM acyltransferase (PatA) is an essential membrane associated acyltransferase, it transfers a palmitoyl moiety from palmitoyl-CoA to the 6-position of the mannose ring linked to 2-position of inositol in PIM1/PIM2 resulting in Ac1PIM1 and Ac1PIM2 |
-, 756084 |
