9DXV
Crystal structure of cobalt-incorporated human 2-aminoethanethiol (aka cysteamine) dioxygenase (ADO) variant C18S/C239S in complex with CP6-L8K-Ser
This is a non-PDB format compatible entry.
Summary for 9DXV
| Entry DOI | 10.2210/pdb9dxv/pdb |
| Descriptor | 2-aminoethanethiol dioxygenase, CP6-L8K-Ser, COBALT (II) ION, ... (7 entities in total) |
| Functional Keywords | oxygen-sensor, thiol dioxygenase, oxidoreductase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 32772.46 |
| Authors | |
| Primary citation | Jiramongkol, Y.,Patel, K.,Johansen-Leete, J.,Maxwell, J.W.C.,Chang, Y.,Du, J.J.,Passioura, T.,Cook, K.M.,Payne, R.J.,White, M.D. An mRNA-display derived cyclic peptide scaffold reveals the substrate binding interactions of an N-terminal cysteine oxidase. Nat Commun, 16:4761-4761, 2025 Cited by PubMed Abstract: N-terminal cysteine oxidases (NCOs) act as enzymatic oxygen (O) sensors, coordinating cellular changes to hypoxia in animals and plants. They regulate the O-dependent stability of proteins bearing an N-terminal cysteine residue through the N-degron pathway. Despite their important role in hypoxic adaptation, which renders them potential therapeutic and agrichemical targets, structural information on NCO substrate binding remains elusive. To overcome this challenge, we employed a unique strategy by which a cyclic peptide inhibitor of the mammalian NCO, 2-aminoethanethiol dioxygenase (ADO), was identified by mRNA display and used as a scaffold to graft substrate moieties. This allowed the determination of two substrate analogue-bound crystal structures of ADO. Key binding interactions were revealed, including bidentate coordination of the N-terminal residue at the metal cofactor. Subsequent structure guided mutagenesis identified aspartate-206 as an essential catalytic residue, playing a role in reactive oxygen intermediate orientation or stabilisation. These findings provide fundamental information on ADO substrate interactions, which can elucidate enzyme mechanism and act as a platform for chemical discovery. PubMed: 40404614DOI: 10.1038/s41467-025-59960-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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