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Crystal structure of the pyoverdine maturation protein PvdP in complex with the mock substrates L-tyrosine and zinc.Crystal structure of the pyoverdine maturation protein PvdP in complex with the mock substrates L-tyrosine and zinc.
Structural highlights
Publication Abstract from PubMedPyoverdines (PVDs) are important chromophore-containing siderophores of fluorescent pseudomonad bacteria such as the opportunistic human pathogen Pseudomonas aeruginosa, in which they play an essential role in host infection. PVD biosynthesis encompasses a complex pathway comprising cytosolic non-ribosomal peptide synthetases which produce a polypeptide precursor that periplasmic enzymes convert to the final product. The structures of most enzymes involved in PVD chromophore maturation have been elucidated, but the structure of the essential tyrosinase PvdP, a monooxygenase required for the penultimate step in PVD biosynthesis, is not known. Here, we closed this gap by determining the crystal structure of PvdP in an apo- and tyrosine-complexed state at 2.1 and 2.7 A, respectively. These structures revealed that PvdP is a homodimer, with each chain consisting of a C-terminal tyrosinase domain and an N-terminal eight-stranded beta-barrel reminiscent of streptavidin that appears to have a structural role only. We observed that ligand binding leads to the displacement of a "placeholder" tyrosine that blocks the active site in the apo structure. This exposes a large, deep binding site that seems suitable for accommodating ferribactin, a substrate of PvdP in PVD biosynthesis. The binding site consists almost exclusively of residues from the tyrosinase domain. Of note, we also found that this domain is more closely related to tyrosinases from arthropods rather than to tyrosinases from other bacteria. In conclusion, our work unravels the structural basis of PvdP's activity in PVD biosynthesis, observations that may inform structure-guided development of PvdP-specific inhibitors to manage P. aeruginosa infections. Pseudomonas aeruginosa pyoverdine maturation enzyme PvdP has a noncanonical domain architecture and affords insight into a new subclass of tyrosinases.,Poppe J, Reichelt J, Blankenfeldt W J Biol Chem. 2018 Jul 20. pii: RA118.002560. doi: 10.1074/jbc.RA118.002560. PMID:30030378[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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