3ite
From Proteopedia
The third adenylation domain of the fungal SidN non-ribosomal peptide synthetase
Structural highlights
FunctionSIDN_EPIFI Nonribosomal peptide synthase required for the biosynthetis of epichloenin A, an extracellular siderophore that plays a crucial role in endophyte-grass symbioses (PubMed:19923209, PubMed:23658520). SidN assembles epichloenin A by activating and incorporating three trans-anhydromevalonylhydroxyornithine (trans-AMHO), 1 glutamine and 4 glycine moieties (PubMed:23658520). Trans-AMHO is produced from L-ornithine via 2 steps involving a L-ornithine N(5)-monooxygenase and an AHMO-N(5)-transacylase that have still to be identified (PubMed:19923209). The third adenylation domain (A3) of sidN incorporates the hydroxamate groups of the siderophore which forms an octahedral iron complex (PubMed:19923209). The other component amino acids are assembled by sidN adenylation domains A1 and A2 (PubMed:19923209, PubMed:23658520).[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNonribosomal peptide synthetases (NRPSs) are large, multidomain proteins that are involved in the biosynthesis of an array of secondary metabolites. We report the structure of the third adenylation domain from the siderophore-synthesizing NRPS, SidN, from the endophytic fungus Neotyphodium lolii. This is the first structure of a eukaryotic NRPS domain, and it reveals a large binding pocket required to accommodate the unusual amino acid substrate, N(delta)-cis-anhydromevalonyl-N(delta)-hydroxy-L-ornithine (cis-AMHO). The specific activation of cis-AMHO was confirmed biochemically, and an AMHO moiety was unambiguously identified as a component of the fungal siderophore using mass spectroscopy. The protein structure shows that the substrate binding pocket is defined by 17 amino acid residues, in contrast to both prokaryotic adenylation domains and to previous predictions based on modeling. Existing substrate prediction methods for NRPS adenylation domains fail for domains from eukaryotes due to the divergence of their signature sequences from those of prokaryotes. Thus, this new structure will provide a basis for improving prediction methods for eukaryotic NRPS enzymes that play important and diverse roles in the biology of fungi. Structure of a eukaryotic nonribosomal peptide synthetase adenylation domain that activates a large hydroxamate amino acid in siderophore biosynthesis.,Lee TV, Johnson LJ, Johnson RD, Koulman A, Lane GA, Lott JS, Arcus VL J Biol Chem. 2010 Jan 22;285(4):2415-27. Epub 2009 Nov 18. PMID:19923209[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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