Structural basis for lipid binding and mechanism of the Mycobacterium tuberculosis Rv3802 phospholipase

Christopher M. Goins, Celine M. Schreidah, Steven Dajnowicz, Donald R. Ronning

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


The Mycobacterium tuberculosis rv3802c gene encodes an essential enzyme with thioesterase and phospholipase A activity. Overexpression of Rv3802 orthologs in Mycobacterium smegmatis and Corynebacterium glutamicum increases mycolate content and decreases glycerophospholipids. Although a role in modulating the lipid composition of the unique mycomembrane has been proposed, the true biological function of Rv3802 remains uncertain. In this study, we present the first M. tuberculosis Rv3802 X-ray crystal structure, solved to 1.7 Å resolution. On the basis of the binding of PEG molecules to Rv3802, we identified its lipid-binding site and the structural basis for phosphatidyl-based substrate binding and phospholipase A activity. We found that movement of the α8-helix affords lipid binding and is required for catalytic turnover through covalent tethering. We gained insights into the mechanism of acyl hydrolysis by observing differing arrangements of PEG and water molecules within the active site. This study provides structural insights into biological function and facilitates future structure-based drug design toward Rv3802.

Original languageEnglish (US)
Pages (from-to)1363-1372
Number of pages10
JournalJournal of Biological Chemistry
Issue number4
StatePublished - Jan 26 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Structural basis for lipid binding and mechanism of the Mycobacterium tuberculosis Rv3802 phospholipase'. Together they form a unique fingerprint.

Cite this