6uts

Crystal Structure of bacterial pirin YhhW in complex with nickel(II) from Escherichia coli

spinqualitylabelsall models 6uts, resolution 3.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6uts is a 1 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.09Å Ligands: NI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function YHHW_ECOLI Has quercetin 2,3-dioxygenase activity in vitro. Its physiological role is unknown; however, may provide a mechanism that would avoid inhibition of key cellular proteins, such as DNA gyrase, by quercetin. Publication Abstract from PubMed Pirin is a nonheme metalloprotein that occurs widely in human tissues and is highly conserved across all taxa. Pirin proteins typically function as nuclear transcription regulators, but two Pirin orthologs, YhhW (from Escherichia coli) and hPirin (from humans) were revealed to possess enzymatic activity of degrading quercetin. The exact role of Pirin homologues and their catalytic specificity remain poorly understood. In this work, by screening against a panel of plant flavonoids, we found that both Pirins catalyze the oxidative degradation of a wide spectrum of flavonol analogues and release carbon monoxide (CO) in the process. This shows that Pirin acts on a broad range of substrates and could represent a novel dietary source of CO in vivo. Although the kinetic profiles differ substantially between two Pirins, the identified substrate structures all share a 2,3-double bond and 3-hydroxyl and 4-oxo groups on their "flavonol backbone," which contribute to the specific enzyme-substrate interaction. While hPirin is iron-dependent, YhhW is identified as a novel nickel-containing dioxygenase member of the bicupin family. Besides the expanded Pirin activity, we present the crystal structures of the native Ni-YhhW and tag-free Fe-hPirin, revealing the distinctive differences occurring at the metal-binding site. In addition, YhhW features a flexible Omega-loop near the catalytic cavity, which may help stabilize the reaction intermediates via a Ni-flavonol complex. The structure-dependent modulation of substrate binding to the catalytic cavity adds to understanding the differential dispositions of natural flavonols by human and bacterial Pirins. Structure-Dependent Modulation of Substrate Binding and Biodegradation Activity of Pirin Proteins toward Plant Flavonols.,Guo B, Zhang Y, Hicks G, Huang X, Li R, Roy N, Jia Z ACS Chem Biol. 2019 Oct 23. doi: 10.1021/acschembio.9b00575. PMID:31609578 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase 3D structures

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