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ACS Chem Biol. 2017 Mar 17;12(3):643-647. doi: 10.1021/acschembio.7b00031. Epub 2017 Feb 15.

Substrate Trapping in the Siderophore Tailoring Enzyme PvdQ.

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Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
Department of Chemistry and Biochemistry, Loyola University Chicago , Chicago, Illinois 60660, United States.
Hauptman-Woodward Medical Research Institute and Department of Structural Biology, SUNY University at Buffalo , Buffalo, New York 14203, United States.


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.

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