6dnu

Crystal Structure of Neisseria meningitidis DsbD c-terminal domain in the oxidised form

spinqualitylabelsall models 6dnu, resolution 2.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6dnu is a 2 chain structure with sequence from Neiml. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: P6G Gene: dsbD, NMO_1340 (NEIML) Activity: Protein-disulfide reductase, with EC number 1.8.1.8 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [C6S7X6_NEIML] Required to facilitate the formation of correct disulfide bonds in some periplasmic proteins and for the assembly of the periplasmic c-type cytochromes. Acts by transferring electrons from cytoplasmic thioredoxin to the periplasm. This transfer involves a cascade of disulfide bond formation and reduction steps.[HAMAP-Rule:MF_00399] Publication Abstract from PubMed The worldwide incidence of neisserial infections, particularly gonococcal infections, is increasingly associated with antibiotic resistant strains. In particular, extensively drug-resistant Neisseria gonorrhoeae strains that are resistant to third-generation cephalosporins are a major public health concern. There is a pressing clinical need to identify new targets for the development of antibiotics effective against neisserial-specific processes. In this study, we report that the bacterial disulfide reductase DsbD is highly prevalent and conserved amongst Neisseria spp. and that this enzyme is essential for survival of N. gonorrhoeae DsbD is a membrane bound protein that consists of two periplasmic domains, n-DsbD and c-DsbD, which flank the transmembrane domain t-DsbD. In the current work we show that the two functionally essential periplasmic domains of Neisseria DsbD catalyze electron transfer reactions through unidirectional inter-domain interactions, from reduced c-DsbD to oxidized n-DsbD, and that this process is not dictated by their redox potentials. Structural characterization of Neisseria n- and c-DsbD domains in both redox states provides evidence that steric hindrance reduces interactions between the two periplasmic domains when n-DsbD is reduced, thereby preventing a futile redox cycle. Finally, we propose a conserved mechanism of electron transfer for DsbD and define the residues involved in domain-domain recognition. Inhibitors of the interaction of the two DsbD domains have the potential to be developed as anti-neisserial agents. Structural and biochemical insights into the disulfide reductase mechanism of DsbD, an essential enzyme for neisserial pathogens.,Smith RP, Mohanty B, Mowlaboccus S, Paxman JJ, Williams ML, Headey SJ, Wang G, Subedi P, Doak BC, Kahler CM, Scanlon MJ, Heras B J Biol Chem. 2018 Sep 4. pii: RA118.004847. doi: 10.1074/jbc.RA118.004847. PMID:30181210 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thiol:disulfide interchange protein

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