Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in Mycobacterium tuberculosis

Gérald Larrouy-Maumus, Tapan Biswas, Debbie M. Hunt, Geoff Kelly, Oleg V. Tsodikov, Luiz Pedro Soŕio De Carvalho

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Functional assignment of enzymes encoded by the Mycobacterium tuberculosis genome is largely incomplete despite recent advances in genomics and bioinformatics. Here, we applied an activity-based metabolomic profiling method to assign function to a unique phosphatase, Rv1692. In contrast to its annotation as a nucleotide phosphatase, metabolomic profiling and kinetic characterization indicate that Rv1692 is a D,L-glycerol 3-phosphate phosphatase. Crystal structures of Rv1692 reveal a unique architecture, a fusion of a predicted haloacid dehalogenase fold with a previously unidentified GCN5-related N-acetyltransferase region. Although not directly involved in acetyl transfer, or regulation of enzymatic activity in vitro, this GCN5-related N-acetyltransferase region is critical for the solubility of the phosphatase. Structural and biochemical analysis shows that the active site features are adapted for recognition of small polyol phosphates, and not nucleotide substrates. Functional assignment and metabolomic studies of M. tuberculosis lacking rv1692 demonstrate that Rv1692 is the final enzyme involved in glycerophospholipid recycling/catabolism, a pathway not previously described in M. tuberculosis.

Original languageEnglish
Pages (from-to)11320-11325
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number28
DOIs
StatePublished - Jul 9 2013

Keywords

  • Enzyme function
  • Haloacid dehalogenase superfamily
  • Pathway discovery

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in Mycobacterium tuberculosis'. Together they form a unique fingerprint.

Cite this