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Literature summary extracted from

  • Boldrin, F.; Anso, I.; Alebouyeh, S.; Sevilla, I.A.; Geijo, M.; Garrido, J.M.; Marina, A.; Cioetto Mazzabo, L.; Segafreddo, G.; Guerin, M.E.; Manganelli, R.; Prados-Rosales, R.
    The phosphatidyl-myo-inositol dimannoside acyltransferase PatA is essential for Mycobacterium tuberculosis growth in vitro and in vivo (2021), J. Bacteriol., 203, e00439-20.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.3.1.265 drug development enzyme PatA is a target for drug discovery programs against the major human pathogen, Mycobacterium tuberculosis. The mycobacterial cell envelope, with phosphatidyl-myo-inositol mannosides (PIMs) as key virulence factors and important components of the cell envelope, is a major factor in this intrinsic drug resistance Mycobacterium tuberculosis

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.265 gene patA or Rv2611c, patA is part of a predicted operon including pimA (rv2610c) and rv2609c, quantitative reverse transcription PCR enzyme expression analysis Mycobacterium tuberculosis

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.265 additional information construction of a patA conditional mutant strain TB506.1, silencing of patA is bactericidal in batch cultures. Level of pimA expression remains unaltered in the strain in absence of anhydrotetracycline, while in presence of anhydrotetracycline, pimA is exclusively repressed in mutant strain TB99 and patA is exclusively repressed in TB506.1.The mRNA levels of rv2612c remain constant in strains TB99 and TB506.1. The phenotype is associated with significantly reduced levels of Ac1PIM2, an important structural component of the mycobacterial inner membrane. During macrophage infection and in a mouse model of infection, a dramatic decrease in viable counts is observed upon silencing of the patA gene. Production of PIM is greatly reduced in patA-depleted mycobacteria Mycobacterium tuberculosis

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.1.265 membrane membrane-associated on the cytosolic side Mycobacterium tuberculosis 16020
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Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.265 2,6-O-bis(alpha-D-mannopyranosyl)-1-phosphatidyl-1D-myo-inositol + palmitoyl-CoA Mycobacterium tuberculosis
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 2-O-(alpha-D-mannosyl)-6-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol + CoA
-
 ?
2.3.1.265 2,6-O-bis(alpha-D-mannopyranosyl)-1-phosphatidyl-1D-myo-inositol + palmitoyl-CoA Mycobacterium tuberculosis H37Rv
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 2-O-(alpha-D-mannosyl)-6-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol + CoA
-
 ?
2.3.1.265 2,6-O-bis(alpha-D-mannopyranosyl)-1-phosphatidyl-1D-myo-inositol + palmitoyl-CoA Mycobacterium tuberculosis ATCC 25618
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 2-O-(alpha-D-mannosyl)-6-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol + CoA
-
 ?
2.3.1.265 palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol Mycobacterium tuberculosis
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 CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol
-
 ?
2.3.1.265 palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol Mycobacterium tuberculosis H37Rv
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 CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol
-
 ?
2.3.1.265 palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol Mycobacterium tuberculosis ATCC 25618
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 CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.265 Mycobacterium tuberculosis P9WMB5
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-
2.3.1.265 Mycobacterium tuberculosis ATCC 25618 P9WMB5
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2.3.1.265 Mycobacterium tuberculosis H37Rv P9WMB5
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Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.265 2,6-O-bis(alpha-D-mannopyranosyl)-1-phosphatidyl-1D-myo-inositol + palmitoyl-CoA
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 Mycobacterium tuberculosis 2-O-(alpha-D-mannosyl)-6-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol + CoA
-
 ?
2.3.1.265 2,6-O-bis(alpha-D-mannopyranosyl)-1-phosphatidyl-1D-myo-inositol + palmitoyl-CoA
-
 Mycobacterium tuberculosis H37Rv 2-O-(alpha-D-mannosyl)-6-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol + CoA
-
 ?
2.3.1.265 2,6-O-bis(alpha-D-mannopyranosyl)-1-phosphatidyl-1D-myo-inositol + palmitoyl-CoA
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 Mycobacterium tuberculosis ATCC 25618 2-O-(alpha-D-mannosyl)-6-O-(6-O-palmitoyl-alpha-D-mannosyl)-1-phosphatidyl-1D-myo-inositol + CoA
-
 ?
2.3.1.265 palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol
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 Mycobacterium tuberculosis CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol
-
 ?
2.3.1.265 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
-
 ?
2.3.1.265 palmitoyl-CoA + 2,6-di-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol
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 Mycobacterium tuberculosis ATCC 25618 CoA + 2-O-(6-O-palmitoyl-alpha-D-mannosyl)-6-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.265 PatA
-
 Mycobacterium tuberculosis
2.3.1.265 phosphatidyl-myo-inositol dimannoside acyltransferase
-
 Mycobacterium tuberculosis
2.3.1.265 phosphatidylinositol mannoside acyltransferase SwissProt Mycobacterium tuberculosis
2.3.1.265 PIM acyltransferase SwissProt Mycobacterium tuberculosis
2.3.1.265 Rv2611c
-
 Mycobacterium tuberculosis

Expression

EC Number Organism Comment Expression
2.3.1.265 Mycobacterium tuberculosis patA expression is downregulated by anhydrotetracycline down

General Information

EC Number General Information Comment Organism
2.3.1.265 malfunction silencing of patA in axenic cultures results in bacterial death. Production of PIM is greatly reduced in patA-depleted mycobacteria. In strain TB506.1, a reduction is observed in lipid bands I, II, and III, corresponding to Ac1PIM6, Ac2PIM6, and Ac1PIM2, respectively Mycobacterium tuberculosis
2.3.1.265 metabolism PatA is a membrane-associated acyltransferase that transfers a palmitoyl moiety from palmitoyl coenzyme A (palmitoyl-CoA) to the 6-position of the mannose ring linked to the 2-position of inositol in PIM1/PIM2. PIMs are based on a phosphatidyl-myo-inositol (PI) anchor and can contain one to six mannose residues and up to four acyl chains. The tri- and tetra-acylated phosphatidyl-myo-inositol dimannosides (Ac1PIM2 and Ac2PIM2, respectively) are considered both metabolic end products and intermediates in the biosynthesis of the tri- and tetra-phosphatidyl-myo-inositol hexamannosides (Ac1PIM6 and Ac2PIM6, respectively), lipomannan (LM), and lipoarabinomannan (LAM) Mycobacterium tuberculosis
2.3.1.265 additional information lipid profile characterization by thin-layer chromatography Mycobacterium tuberculosis
2.3.1.265 physiological function Mycobacterium tuberculosis comprises an unusual cell envelope dominated by unique lipids and glycans that provides a permeability barrier against hydrophilic drugs and is central for its survival and virulence. Phosphatidyl-myo-inositol mannosides (PIMs) are glycolipids considered to be not only key structural components of the cell envelope but also precursors of lipomannan (LM) and lipoarabinomannan (LAM), important lipoglycans implicated in host-pathogen interactions. PatA is a membrane-associated acyltransferase that transfers a palmitoyl moiety from palmitoyl coenzyme A (palmitoyl-CoA) to the 6-position of the mannose ring linked to the 2-position of inositol in PIM1/PIM2. The function of PatA is vital for Mycobacterium tuberculosis in vitro and in vivo, requirement of PatA for viability. Gene patA is essential for growth in macrophages and in mice Mycobacterium tuberculosis