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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
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Structural basis of phosphatidyl-myo-inositol mannosides biosynthesis in mycobacteria

Enea Sancho-Vaello1, David Albesa-Jové2, Ane Rodrigo-Unzueta1

  • 1Unidad de Biofísica, Centro Mixto Consejo Superior de Investigaciones Científicas, Universidad del País Vasco, Leioa, Bizkaia 48940, Spain; Departamento de Bioquímica, Universidad del País Vasco, Leioa, Bizkaia 48940, Spain; Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC, UPV/EHU), Barrio Sarriena s/n, Leioa, Bizkaia 48940, Spain.

Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
|November 10, 2016
PubMed

Insights

Phosphatidyl-myo-inositol mannosides (PIMs) are essential glycolipids in Mycobacterium. Their biosynthetic pathway involves key enzymes like PIPS, PMT A/B, and PatA, crucial for understanding host-pathogen interactions.

Area of Science:

  • Microbiology
  • Glycolipid Biochemistry
  • Host-Pathogen Interactions

Background:

  • Phosphatidyl-myo-inositol mannosides (PIMs) are unique glycolipids found in Mycobacterium cell envelopes.
  • PIMs are essential structural components and precursors to lipomannan and lipoarabinomannan.
  • These lipoglycans play critical roles in host-pathogen interactions.

Purpose of the Study:

  • To elucidate the molecular basis of the PIM biosynthetic pathway.
  • To characterize key enzymes involved in early PIM synthesis.
  • To provide insights into the structural and functional roles of PIMs.

Main Methods:

  • Structural characterization of integral membrane enzymes.
  • Biochemical analysis of enzymes at the protein-membrane interface.
  • Investigating the early steps of the PIM pathway.

Main Results:

  • The integral membrane enzyme phosphatidyl-myo-inositol phosphate synthase (PIPS) was structurally characterized.
  • Three enzymes, phosphatidyl-myo-inositol mannosyltransferases A and B (PMT A/B) and acyltransferase PatA, were characterized.
  • These enzymes establish the foundation for understanding the early stages of PIM biosynthesis.

Conclusions:

  • The characterization of PIPS, PMT A/B, and PatA provides a molecular understanding of the initial steps in PIM synthesis.
  • This knowledge is vital for comprehending the assembly of the Mycobacterium cell envelope.
  • Further research into PIMs can offer targets for therapeutic interventions against mycobacterial infections.
Keywords:
AcyltransferaseGlycolipidGlycosyltransferaseMycobacteriaPhosphatidylinositol mannosidesStructural biology

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