3L94: Structure Of Pvdq Covalently Acylated With Myristate

Citation:
Abstract
The human pathogen Pseudomonas aeruginosa produces a variety of virulence factors including pyoverdine, a nonribosomally produced peptide siderophore. The maturation pathway of the pyoverdine peptide is complex and provides a unique target for inhibition. Within the pyoverdine biosynthetic cluster is a periplasmic hydrolase, PvdQ, that is required for pyoverdine production. However, the precise role of PvdQ in the maturation pathway has not been biochemically characterized. We demonstrate herein that the initial module of the nonribosomal peptide synthetase PvdL adds a myristate moiety to the pyoverdine precursor. We extracted this acylated precursor, called PVDIq, from a pvdQ mutant strain and show that the PvdQ enzyme removes the fatty acid catalyzing one of the final steps in pyoverdine maturation. Incubation of PVDIq with crystals of PvdQ allowed us to capture the acylated enzyme and confirm through structural studies the chemical composition of the incorporated acyl chain. Finally, because inhibition of siderophore synthesis has been identified as a potential antibiotic strategy, we developed a high-throughput screening assay and tested a small chemical library for compounds that inhibit PvdQ activity. Two compounds that block PvdQ have been identified, and their binding within the fatty acid binding pocket was structurally characterized.
PDB ID: 3L94Download
MMDB ID: 88209
PDB Deposition Date: 2010/1/4
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 3L94: dimeric; determined by author and by software (PISA)
Molecular Components in 3L94
Label Count Molecule
Proteins (2 molecules)
1
Acyl-homoserine Lactone Acylase Pvdq Subunit Alpha(Gene symbol: pvdQ)
Molecule annotation
1
Acyl-homoserine Lactone Acylase Pvdq Subunit Beta(Gene symbol: pvdQ)
Molecule annotation
Chemicals (20 molecules)
1
19
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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