6dps: Difference between revisions

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 ==Crystal Structure of Neisseria meningitidis DsbD n-terminal domain in the oxidised form==
-<StructureSection load='6dps' size='340' side='right' caption='[[6dps]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
+<StructureSection load='6dps' size='340' side='right'caption='[[6dps]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6dps]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DPS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6dps]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis_alpha14 Neisseria meningitidis alpha14]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DPS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.556&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-disulfide_reductase Protein-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.8 1.8.1.8] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dps OCA], [http://pdbe.org/6dps PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dps RCSB], [http://www.ebi.ac.uk/pdbsum/6dps PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dps ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6dps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dps OCA], [https://pdbe.org/6dps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dps RCSB], [https://www.ebi.ac.uk/pdbsum/6dps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dps ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/C6S7X6_NEIML 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]
+[https://www.uniprot.org/uniprot/C6S7X6_NEIML 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]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-The membrane protein DsbD is a reductase that acts as an electron hub, translocating reducing equivalents from cytoplasmic thioredoxin to a number of periplasmic substrates involved in oxidative protein folding, cytochrome c maturation and oxidative stress defence. DsbD is a multi-domain protein consisting of a transmembrane domain (t-DsbD) flanked by two periplasmic domains (n-DsbD and c-DsbD). Previous studies have shown that DsbD is required for the survival of the obligate human pathogen Neisseria meningitidis. To help understand the structural and functional aspects of N. meningitidis DsbD, the two periplasmic domains which are required for electron transfer are being studied. Here, the expression, purification and biophysical properties of n-NmDsbD and c-NmDsbD are described. The crystallization and crystallographic analysis of n-NmDsbD and c-NmDsbD are also described in both redox states, which differ only in the presence or absence of a disulfide bond but which crystallized in completely different conditions. Crystals of n-NmDsbDOx, n-NmDsbDRed, c-NmDsbDOx and c-NmDsbDRed diffracted to 2.3, 1.6, 2.3 and 1.7 A resolution and belonged to space groups P213, P321, P41 and P1211, respectively.
+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.
-Production, biophysical characterization and initial crystallization studies of the N- and C-terminal domains of DsbD, an essential enzyme in Neisseria meningitidis.,Smith RP, Whitten AE, Paxman JJ, Kahler CM, Scanlon MJ, Heras B Acta Crystallogr F Struct Biol Commun. 2018 Jan 1;74(Pt 1):31-38. doi:, 10.1107/S2053230X17017800. Epub 2018 Jan 1. PMID:29372905<ref>PMID:29372905</ref>
+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<ref>PMID:30181210</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
 <div class="pdbe-citations 6dps" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Thiol:disulfide interchange protein 3D structures|Thiol:disulfide interchange protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Protein-disulfide reductase]]
+[[Category: Large Structures]]
-[[Category: Heras, B]]
+[[Category: Neisseria meningitidis alpha14]]
-[[Category: Paxman, J J]]
+[[Category: Heras B]]
-[[Category: Smith, R P]]
+[[Category: Paxman JJ]]
-[[Category: Disulphide reductase]]
+[[Category: Smith RP]]
-[[Category: Dsb protein]]
-[[Category: Oxidoreductase]]