7LVZ

Crystal structure of ADO

Summary for 7LVZ

• Entry DOI: 10.2210/pdb7lvz/pdb
• Descriptor: 2-aminoethanethiol dioxygenase, FE (II) ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: cupin dioxygenase cysteine oxidation non-heme iron enzyme, oxidoreductase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 4
• Total formula weight: 114039.57

Authors

Bingman, C.A.,Fernandez, R.L.,Smith, R.W.,Fox, B.G.,Brunold, T.C. (deposition date: 2021-02-26, release date: 2022-01-05, Last modification date: 2024-04-03)

Primary citation

Fernandez, R.L.,Elmendorf, L.D.,Smith, R.W.,Bingman, C.A.,Fox, B.G.,Brunold, T.C.
The Crystal Structure of Cysteamine Dioxygenase Reveals the Origin of the Large Substrate Scope of This Vital Mammalian Enzyme.
Biochemistry, 60:3728-3737, 2021

PubMed Abstract: We report the crystal structure of the mammalian non-heme iron enzyme cysteamine dioxygenase (ADO) at 1.9 Å resolution, which shows an Fe and three-histidine (3-His) active site situated at the end of a wide substrate access channel. The open approach to the active site is consistent with the recent discovery that ADO catalyzes not only the conversion of cysteamine to hypotaurine but also the oxidation of N-terminal cysteine (Nt-Cys) peptides to their corresponding sulfinic acids as part of the eukaryotic N-degron pathway. Whole-protein models of ADO in complex with either cysteamine or an Nt-Cys peptide, generated using molecular dynamics and quantum mechanics/molecular mechanics calculations, suggest occlusion of access to the active site by peptide substrate binding. This finding highlights the importance of a small tunnel that leads from the opposite face of the enzyme into the active site, providing a path through which co-substrate O could access the Fe center. Intriguingly, the entrance to this tunnel is guarded by two Cys residues that may form a disulfide bond to regulate O delivery in response to changes in the intracellular redox potential. Notably, the Cys and tyrosine residues shown to be capable of forming a cross-link in human ADO reside ∼7 Å from the iron center. As such, cross-link formation may not be structurally or functionally significant in ADO.

PubMed: 34762398
DOI: 10.1021/acs.biochem.1c00463

Experimental method

X-RAY DIFFRACTION (1.89 Å)