Substrate Trapping in the Siderophore Tailoring Enzyme PvdQ.
Kenneth D ClevengerRomila MascarenhasDaniel CatlinRui WuMichael P SnyderEric J DrakeAndrew M GulickDali LiuWalter FastPublished in: ACS chemical biology (2017)
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.
Keyphrases
- wild type
- pseudomonas aeruginosa
- crystal structure
- biofilm formation
- cystic fibrosis
- staphylococcus aureus
- healthcare
- single molecule
- high resolution
- dna binding
- structural basis
- emergency department
- amino acid
- binding protein
- current status
- adverse drug
- drug induced
- mass spectrometry
- drug resistant
- electronic health record
- dual energy