Abstract
Bacterial pathogens need to scavenge iron from their host for growth and proliferation during infection. They have evolved several strategies to do this, one being the biosynthesis and excretion of small, high-affinity iron chelators known as siderophores. The biosynthesis of siderophores is an important area of study, not only for potential therapeutic intervention but also to illuminate new enzyme chemistries. Two general pathways for siderophore biosynthesis exist: the well-characterized nonribosomal peptide synthetase (NRPS)-dependent pathway and the NRPS-independent siderophore (NIS) pathway, which relies on a different family of sparsely investigated synthetases. Here we report structural and biochemical studies of AcsD from Pectobacterium (formerly Erwinia) chrysanthemi, an NIS synthetase involved in achromobactin biosynthesis. The structures of ATP and citrate complexes provide a mechanistic rationale for stereospecific formation of an enzyme-bound (3R)-citryladenylate, which reacts with L-serine to form a likely achromobactin precursor. AcsD is a unique acyladenylate-forming enzyme with a new fold and chemical catalysis strategy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Base Sequence
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Biocatalysis
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Chromatography, High Pressure Liquid
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Citric Acid / chemistry
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Citric Acid / metabolism*
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DNA Primers
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Dickeya chrysanthemi / metabolism*
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Mutagenesis, Site-Directed
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Protein Conformation
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Siderophores / biosynthesis*
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Spectrometry, Mass, Electrospray Ionization
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Stereoisomerism
Substances
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Bacterial Proteins
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DNA Primers
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Siderophores
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Citric Acid
Associated data
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PDB/2W02
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PDB/2W03
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PDB/2W04
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PDB/3FFE
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PubChem-Substance/56437638
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PubChem-Substance/56437639
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PubChem-Substance/56437640
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PubChem-Substance/56437641
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PubChem-Substance/56437642
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PubChem-Substance/56437643
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PubChem-Substance/56437644
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PubChem-Substance/56437645
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PubChem-Substance/56437646
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PubChem-Substance/56437647
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PubChem-Substance/56437648
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PubChem-Substance/56437649
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PubChem-Substance/56437650
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PubChem-Substance/56437651
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PubChem-Substance/56437652
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PubChem-Substance/56437653
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PubChem-Substance/56437654
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PubChem-Substance/56437655
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PubChem-Substance/56437656
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PubChem-Substance/56437657
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PubChem-Substance/56437658
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PubChem-Substance/56437659
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PubChem-Substance/56437660
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PubChem-Substance/56437661
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PubChem-Substance/56437662
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PubChem-Substance/56437663
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PubChem-Substance/56437664
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PubChem-Substance/56437665
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PubChem-Substance/56437666
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PubChem-Substance/56437667
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PubChem-Substance/56437668
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PubChem-Substance/56437669
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PubChem-Substance/56437670
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PubChem-Substance/56437671
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PubChem-Substance/56437672
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PubChem-Substance/56437673
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PubChem-Substance/56437674
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PubChem-Substance/56437675
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PubChem-Substance/56437676