8qq1

SpNOX dehydrogenase domain, mutant F397W in complex with Flavin adenine dinucleotide (FAD)

spinqualitylabelsall models 8qq1, resolution 1.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8qq1 is a 3 chain structure with sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.941Å Ligands: BR, FAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A4J2B4U9_STREE Publication Abstract from PubMed NADPH oxidases (NOX) are transmembrane proteins, widely spread in eukaryotes and prokaryotes, that produce reactive oxygen species (ROS). Eukaryotes use the ROS products for innate immune defense and signaling in critical (patho)physiological processes. Despite the recent structures of human NOX isoforms, the activation of electron transfer remains incompletely understood. SpNOX, a homolog from Streptococcus pneumoniae, can serves as a robust model for exploring electron transfers in the NOX family thanks to its constitutive activity. Crystal structures of SpNOX full-length and dehydrogenase (DH) domain constructs are revealed here. The isolated DH domain acts as a flavin reductase, and both constructs use either NADPH or NADH as substrate. Our findings suggest that hydride transfer from NAD(P)H to FAD is the rate-limiting step in electron transfer. We identify significance of F397 in nicotinamide access to flavin isoalloxazine and confirm flavin binding contributions from both DH and Transmembrane (TM) domains. Comparison with related enzymes suggests that distal access to heme may influence the final electron acceptor, while the relative position of DH and TM does not necessarily correlate with activity, contrary to previous suggestions. It rather suggests requirement of an internal rearrangement, within the DH domain, to switch from a resting to an active state. Thus, SpNOX appears to be a good model of active NOX2, which allows us to propose an explanation for NOX2's requirement for activation. X-ray structure and enzymatic study of a bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX.,Petit-Hartlein I, Vermot A, Thepaut M, Humm AS, Dupeux F, Dupuy J, Chaptal V, Marquez JA, Smith SME, Fieschi F Elife. 2024 Apr 19;13:RP93759. doi: 10.7554/eLife.93759. PMID:38640072 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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