Substrate Trapping in the Siderophore Tailoring Enzyme PvdQ

Kenneth D. Clevenger, Romila Mascarenhas, Daniel Catlin, Rui Wu, Neil L. Kelleher, Eric J. Drake, Andrew M. Gulick, Dali Liu*, Walter Fast

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Siderophore biosynthesis by Pseudomonas aeruginosa enhances virulence and represents an attractive drug target. PvdQ functions in the type-1 pyoverdine biosynthetic pathway by removing a myristoyl anchor from a pyoverdine precursor, allowing eventual release from the periplasm. A circularly permuted version of PvdQ bypasses the self-processing step of this Ntn-hydrolase and retains the activity, selectivity, and structure of wild-type PvdQ, as revealed by a 1.8 Å resolution X-ray crystal structure. A 2.55 Å resolution structure of the inactive S1A/N269D-cpPvdQ mutant in complex with the pyoverdine precursor PVDIq reveals a specific binding pocket for the d-Tyr of this modified peptide substrate. To our knowledge, this structure is the first of a pyoverdine precursor peptide bound to a biosynthetic enzyme. Details of the observed binding interactions have implications for control of pyoverdine biosynthesis and inform future drug design efforts.

Original languageEnglish (US)
Pages (from-to)643-647
Number of pages5
JournalACS chemical biology
Volume12
Issue number3
DOIs
StatePublished - Mar 17 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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