6U4S

wild type cysteine dioxygenase

Summary for 6U4S

• Entry DOI: 10.2210/pdb6u4s/pdb
• Descriptor: Cysteine dioxygenase type 1, FE (III) ION (3 entities in total)
• Functional Keywords: non-heme, dioxygenase, cysteine-tyrosine crosslink, oxidoreductase
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 1
• Total formula weight: 23100.71

Authors

Meneely, K.M.,Chilton, A.S.,Forbes, D.L.,Ellis, H.R.,Lamb, A.L. (deposition date: 2019-08-26, release date: 2020-07-08, Last modification date: 2023-10-11)

Primary citation

Forbes, D.L.,Meneely, K.M.,Chilton, A.S.,Lamb, A.L.,Ellis, H.R.
The 3-His Metal Coordination Site Promotes the Coupling of Oxygen Activation to Cysteine Oxidation in Cysteine Dioxygenase.
Biochemistry, 59:2022-2031, 2020

PubMed Abstract: Cysteine dioxygenase (CDO) structurally resembles cupin enzymes that use a 3-His/1-Glu coordination scheme. However, the glutamate ligand is substituted with a cysteine (Cys93) residue, which forms a thioether bond with tyrosine (Tyr157) under physiological conditions. The reversion variant, C93E CDO, was generated in order to reestablish the more common 3-His/1-Glu metal ligands of the cupin superfamily. This variant provides a framework for testing the structural and functional significance of Cys93 and the cross-link in CDO. Although dioxygen consumption was observed with C93E CDO, it was not coupled with l-cysteine oxidation. Substrate analogues (d-cysteine, cysteamine, and 3-mercaptopropionate) were not viable substrates for the C93E CDO variant, although they showed variable coordinations to the iron center. The structures of C93E and cross-linked and non-cross-linked wild-type CDO were solved by X-ray crystallography to 1.91, 2.49, and 2.30 Å, respectively. The C93E CDO variant had similar overall structural properties compared to cross-linked CDO; however, the iron was coordinated by a 3-His/1-Glu geometry, leaving only two coordination sites available for dioxygen and bidentate l-cysteine binding. The hydroxyl group of Tyr157 shifted in both non-cross-linked and C93E CDO, and this displacement prevented the residue from participating in substrate stabilization. Based on these results, the divergence of the metal center of cysteine dioxygenase from the 3-His/1-Glu geometry seen with many cupin enzymes was essential for effective substrate binding. The substitution of Glu with Cys in CDO allows for a third coordination site on the iron for bidentate cysteine and monodentate oxygen binding.

PubMed: 32368901
DOI: 10.1021/acs.biochem.9b01085

Experimental method

X-RAY DIFFRACTION (2.49 Å)