6bpr

Crystal structure of cysteine, nitric oxide-bound ferrous form of the uncrosslinked F2-Tyr157 human cysteine dioxygenase

spinqualitylabelsall models 6bpr, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bpr is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.96Å Ligands: CYS, F2Y, FE, GOL, NO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CDO1_HUMAN Initiates several important metabolic pathways related to pyruvate and several sulfurate compounds including sulfate, hypotaurine and taurine. Critical regulator of cellular cysteine concentrations. Has an important role in maintaining the hepatic concentation of intracellular free cysteine within a proper narrow range. Publication Abstract from PubMed Cysteine dioxygenase (CDO) is a non-heme iron enzyme that adds two oxygen atoms from dioxygen to the sulfur atom of L-cysteine. Adjacent to the iron site of mammalian CDO, a post-translationally generated Cys-Tyr cofactor is present, whose presence substantially enhances the oxygenase activity. The formation of the Cys-Tyr cofactor in CDO is an autocatalytic process, and it is challenging to study by traditional techniques because the crosslinking reaction is a side, uncoupled, single-turnover oxidation buried among multiple turnovers of L-cysteine oxygenation. Here, we take advantage of our recent success in obtaining a purely uncrosslinked human CDO due to site-specific incorporation 3,5-difluoro-L-tyrosine (F2-Tyr) at the crosslinking site through the genetic code expansion strategy. Using EPR spectroscopy, we show that nitric oxide (*NO), an oxygen surrogate, similarly binds to uncrosslinked F2-Tyr157 CDO as in wild-type human CDO. We determined X-ray crystal structures of uncrosslinked F2-Tyr157 CDO and mature wild-type CDO in complex with both L-cysteine and *NO. These structural data reveal that the active site cysteine (Cys93 in the human enzyme), rather than the generally expected tyrosine (i.e., Tyr157), is well aligned to be oxidized should the normal oxidation reaction uncouple. This structural-based understanding is further supported by a computational study with models built on the uncrosslinked ternary complex structure. Together, these results strongly suggest that the first target to oxidize during the iron-assisted Cys-Tyr cofactor biogenesis is Cys93. Based on these data, a plausible reaction mechanism implementing a cysteine radical involved in the crosslink formation is proposed. Probing the Tyr-Cys Cofactor Biogenesis in Cysteine Dioxygenase by the Genetic Incorporation of Fluorotyrosine.,Li J, Koto T, Davis I, Liu A Biochemistry. 2019 Apr 4. doi: 10.1021/acs.biochem.9b00006. PMID:30946568 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase 3D structures

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