The Three-Dimensional Structure of the Gallium Complex of Azoverdin, a Siderophore of Azomonas macrocytogenes ATCC 12334, Determined by NMR Using Residual Dipolar Coupling Constants

Abstract

In iron-deficient conditions, Azomonas macrocytogenes ATCC 12334 excretes a fluorescent siderophore called azoverdin, which is composed of a six-amino-acid peptide chain linked to a chromophore. Azoverdin chelates iron(III) very strongly, solubilizing it and transporting it back into the cells using an outer-membrane receptor. This compound is related to the pyoverdins, the peptidic siderophores of Pseudomonas, but differs in the site on the chromophore at which the peptide is covalently linked. This feature identifies azoverdin as a member of a new class of pyoverdins: the isopyoverdins. We report the three-dimensional structure of azoverdin-Ga(III) in solution. The use of orientational constraints obtained from the measurement of residual dipolar couplings using samples dissolved in a liquid crystalline medium allowed us to define the absolute configuration of the metal complex, which is Delta. The structure is characterized by a U-shape adopted by the peptide chain, with the N(delta)-acetyl-N(delta)-hydroxyornithine side chains adopting extended conformations in order to chelate the gallium ion. This conformation leaves a large open space permitting access to the gallium ion. The structural consequences of the particular isopyoverdin chemical structure are discussed in the context of the three-dimensional structures of other pyoverdins.

Synthesis, Structure, and Molecular Dynamics of Gallium Complexes of Schizokinen and the Amphiphilic Siderophore Acinetoferrin

“…Trivalent gallium and iron citrates have very similar structures and share the same bidentate coordination mode with the α-hydroxy carboxylic moiety. , Such structural similarity between Fe 3+ and Ga 3+ complexes is typical, for example, for tripodal salicylate-based ligands and has been used in structural studies of several siderophores. − Thus, we anticipate that Fe Af and Fe Sz will have structures very similar to their gallium analogues. The large 8-fold change in partition coefficient upon binding iron indicates that Af is considerably more hydrophobic than Fe Af , despite the facts that metal binding buries six hydrophilic oxygen atoms and there is no net change in molecular charge.…”

Catechol‐Based Biomimetic Functional Materials

“…The ligand properties of enterobactin toward trivalent species (Al III , Ga III , Sc III , In III ),349 and the crystal structure of a enterobactin‐V IV complex have been reported 350. Other natural hydroxamate‐catechol siderophores such as pyoverdin and azoverdin have been shown to form stable coordination complexes with Ga III , Al III ,351, 352 and UO 2 2+ 353. These complexes are so stable that the presence of Al III and Ga III interfere with Fe III absorption in biological media 351.…”

The PvdRT‐OpmQ efflux pump controls the metal selectivity of the iron uptake pathway mediated by the siderophore pyoverdine in Pseudomonas aeruginosa

“…Pyoverdine (PVD) is the principal siderophore produced by the opportunist pathogen Pseudomonas aeruginosa (Schalk, 2008). PVD is a partly cyclic octapeptide linked to a chromophore derived from 2,3‐diamino‐6,7‐dihydroxyquinoline, which renders the siderophore both coloured and fluorescent (Demange et al ., 1990; Wasielewski et al ., 2002). PVD synthesis begins in the bacterial cytoplasm, with the assembly of a non‐fluorescent precursor by non‐ribosomic peptide synthetases (NRPSs) (Visca et al ., 2007), and ends in the periplasm with cyclization of the chromophore moiety (Yeterian et al ., 2010a).…”