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| - | [[Image:1ddt.gif|left|200px]] | |
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| - | <!-- | + | ==THE REFINED STRUCTURE OF DIMERIC DIPHTHERIA TOXIN AT 2.0 ANGSTROMS RESOLUTION== |
| - | The line below this paragraph, containing "STRUCTURE_1ddt", creates the "Structure Box" on the page.
| + | <StructureSection load='1ddt' size='340' side='right'caption='[[1ddt]], [[Resolution|resolution]] 2.00Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1ddt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Corynephage_beta Corynephage beta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DDT FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APU:ADENYLYL-3-5-PHOSPHO-URIDINE-3-MONOPHOSPHATE'>APU</scene></td></tr> |
| - | {{STRUCTURE_1ddt| PDB=1ddt | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ddt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ddt OCA], [https://pdbe.org/1ddt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ddt RCSB], [https://www.ebi.ac.uk/pdbsum/1ddt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ddt ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DTX_CORBE DTX_CORBE] Diphtheria toxin, produced by a phage infecting Corynebacterium diphtheriae, is a proenzyme that, after activation, catalyzes the covalent attachment of the ADP ribose moiety of NAD to eukaryotic elongation factor 2 (eEF-2). Fragment A is the catalytic portion responsible for enzymatic ADP-ribosylation of elongation factor 2, while fragment B is responsible for binding of toxin to cell receptors and entry of fragment A.<ref>PMID:18276581</ref> <ref>PMID:19793133</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The refined structure of dimeric diphtheria toxin (DT) at 2.0 A resolution, based on 37,727 unique reflections (F > 1 sigma (F)), yields a final R factor of 19.5% with a model obeying standard geometry. The refined model consists of 523 amino acid residues, 1 molecule of the bound dinucleotide inhibitor adenylyl 3'-5' uridine 3' monophosphate (ApUp), and 405 well-ordered water molecules. The 2.0-A refined model reveals that the binding motif for ApUp includes residues in the catalytic and receptor-binding domains and is different from the Rossmann dinucleotide-binding fold. ApUp is bound in part by a long loop (residues 34-52) that crosses the active site. Several residues in the active site were previously identified as NAD-binding residues. Glu 148, previously identified as playing a catalytic role in ADP-ribosylation of elongation factor 2 by DT, is about 5 A from uracil in ApUp. The trigger for insertion of the transmembrane domain of DT into the endosomal membrane at low pH may involve 3 intradomain and 4 interdomain salt bridges that will be weakened at low pH by protonation of their acidic residues. The refined model also reveals that each molecule in dimeric DT has an "open" structure unlike most globular proteins, which we call an open monomer. Two open monomers interact by "domain swapping" to form a compact, globular dimeric DT structure. The possibility that the open monomer resembles a membrane insertion intermediate is discussed. |
| | | | |
| - | '''THE REFINED STRUCTURE OF DIMERIC DIPHTHERIA TOXIN AT 2.0 ANGSTROMS RESOLUTION'''
| + | Refined structure of dimeric diphtheria toxin at 2.0 A resolution.,Bennett MJ, Choe S, Eisenberg D Protein Sci. 1994 Sep;3(9):1444-63. PMID:7833807<ref>PMID:7833807</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | The refined structure of dimeric diphtheria toxin (DT) at 2.0 A resolution, based on 37,727 unique reflections (F > 1 sigma (F)), yields a final R factor of 19.5% with a model obeying standard geometry. The refined model consists of 523 amino acid residues, 1 molecule of the bound dinucleotide inhibitor adenylyl 3'-5' uridine 3' monophosphate (ApUp), and 405 well-ordered water molecules. The 2.0-A refined model reveals that the binding motif for ApUp includes residues in the catalytic and receptor-binding domains and is different from the Rossmann dinucleotide-binding fold. ApUp is bound in part by a long loop (residues 34-52) that crosses the active site. Several residues in the active site were previously identified as NAD-binding residues. Glu 148, previously identified as playing a catalytic role in ADP-ribosylation of elongation factor 2 by DT, is about 5 A from uracil in ApUp. The trigger for insertion of the transmembrane domain of DT into the endosomal membrane at low pH may involve 3 intradomain and 4 interdomain salt bridges that will be weakened at low pH by protonation of their acidic residues. The refined model also reveals that each molecule in dimeric DT has an "open" structure unlike most globular proteins, which we call an open monomer. Two open monomers interact by "domain swapping" to form a compact, globular dimeric DT structure. The possibility that the open monomer resembles a membrane insertion intermediate is discussed.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1DDT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Corynephage_beta Corynephage beta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DDT OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1ddt" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Refined structure of dimeric diphtheria toxin at 2.0 A resolution., Bennett MJ, Choe S, Eisenberg D, Protein Sci. 1994 Sep;3(9):1444-63. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7833807 7833807]
| + | *[[Diphtheria toxin|Diphtheria toxin]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Corynephage beta]] | | [[Category: Corynephage beta]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Bennett, M J.]] | + | [[Category: Bennett MJ]] |
| - | [[Category: Eisenberg, D.]] | + | [[Category: Eisenberg D]] |
| - | [[Category: Toxin]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:44:19 2008''
| + | |
| Structural highlights
Function
DTX_CORBE Diphtheria toxin, produced by a phage infecting Corynebacterium diphtheriae, is a proenzyme that, after activation, catalyzes the covalent attachment of the ADP ribose moiety of NAD to eukaryotic elongation factor 2 (eEF-2). Fragment A is the catalytic portion responsible for enzymatic ADP-ribosylation of elongation factor 2, while fragment B is responsible for binding of toxin to cell receptors and entry of fragment A.[1] [2]
Publication Abstract from PubMed
The refined structure of dimeric diphtheria toxin (DT) at 2.0 A resolution, based on 37,727 unique reflections (F > 1 sigma (F)), yields a final R factor of 19.5% with a model obeying standard geometry. The refined model consists of 523 amino acid residues, 1 molecule of the bound dinucleotide inhibitor adenylyl 3'-5' uridine 3' monophosphate (ApUp), and 405 well-ordered water molecules. The 2.0-A refined model reveals that the binding motif for ApUp includes residues in the catalytic and receptor-binding domains and is different from the Rossmann dinucleotide-binding fold. ApUp is bound in part by a long loop (residues 34-52) that crosses the active site. Several residues in the active site were previously identified as NAD-binding residues. Glu 148, previously identified as playing a catalytic role in ADP-ribosylation of elongation factor 2 by DT, is about 5 A from uracil in ApUp. The trigger for insertion of the transmembrane domain of DT into the endosomal membrane at low pH may involve 3 intradomain and 4 interdomain salt bridges that will be weakened at low pH by protonation of their acidic residues. The refined model also reveals that each molecule in dimeric DT has an "open" structure unlike most globular proteins, which we call an open monomer. Two open monomers interact by "domain swapping" to form a compact, globular dimeric DT structure. The possibility that the open monomer resembles a membrane insertion intermediate is discussed.
Refined structure of dimeric diphtheria toxin at 2.0 A resolution.,Bennett MJ, Choe S, Eisenberg D Protein Sci. 1994 Sep;3(9):1444-63. PMID:7833807[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jorgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Rod Merrill A. Cholix toxin, a novel ADP-ribosylating factor from vibrio cholerae. J Biol Chem. 2008 Feb 25;. PMID:18276581 doi:M710008200
- ↑ Turgeon Z, White D, Jorgensen R, Visschedyk D, Fieldhouse RJ, Mangroo D, Merrill AR. Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins. FEMS Microbiol Lett. 2009 Nov;300(1):97-106. Epub 2009 Aug 31. PMID:19793133 doi:10.1111/j.1574-6968.2009.01777.x
- ↑ Bennett MJ, Choe S, Eisenberg D. Refined structure of dimeric diphtheria toxin at 2.0 A resolution. Protein Sci. 1994 Sep;3(9):1444-63. PMID:7833807
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