PXD041103

PXD041103 is an original dataset announced via ProteomeXchange.

Title	The sulfonic-containing peptides (at C281) from trypsin-treated Orf1 in H218O.
Description	Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. Here, we report a non-canonical FAD-dependent enzyme Orf1 that adds a glycine-derived N-formimidoyl group to glycinothricin to form the antibiotic BD-12. X-ray crystallography was used to investigate this complex enzymatic process, which showed Orf1 has two substrate-binding sites that sit 13.5 Å apart unlike canonical FAD-dependent oxidoreductases. One site could accommodate glycine and the other glycinothricin or glycylthricin. Moreover, an intermediate-enzyme adduct with a NOS-covalent linkage was observed in the later site, where it acts as a two-scissile-bond linkage facilitating nucleophilic addition and cofactor-free decarboxylation. The chain length of nucleophilic acceptors vies with bond cleavage sites at either N–O or O–S accounting for N-formimidoylation or N-iminoacetylation. The resultant product is no longer sensitive to aminoglycoside-modifying enzymes, a strategy that antibiotic-producing species employ to counter drug resistance in competing species.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:45:30.803.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041103
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yung-Lin Wang
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-24 19:16:24	ID requested
1	2023-05-10 08:44:36	announced
⏵ 2	2023-11-14 08:45:41	announced	2023-11-14: Updated project metadata.

10.6019/PXD041103;

Wang YL, Chang CY, Hsu NS, Lo IW, Lin KH, Chen CL, Chang CF, Wang ZC, Ogasawara Y, Dairi T, Maruyama C, Hamano Y, Li TL, N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry. Nat Commun, 14(1):2528(2023) [pubmed]

submitter keyword: N-formimmidolation and iminoacetylation enzyme

Tsung-Lin Li
contact affiliation	Genomics Research Center, Academia Sinica, Taipei, 11529 Taiwan
contact email	tlli@gate.sinica.edu.tw
lab head
Yung-Lin Wang
contact affiliation	Genomics Research Center, Academia Sinica
contact email	hcvns3@gate.sinica.edu.tw
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041103
     1. Label: PRIDE project
     2. Name: The sulfonic-containing peptides (at C281) from trypsin-treated Orf1 in H218O.