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| - | [[Image:1mdt.gif|left|200px]] | |
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| - | <!-- | + | ==THE REFINED STRUCTURE OF MONOMERIC DIPHTHERIA TOXIN AT 2.3 ANGSTROMS RESOLUTION== |
| - | The line below this paragraph, containing "STRUCTURE_1mdt", creates the "Structure Box" on the page. | + | <StructureSection load='1mdt' size='340' side='right'caption='[[1mdt]], [[Resolution|resolution]] 2.30Å' 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'>[[1mdt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Corynephage_beta Corynephage beta]. The September 2005 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Cholera Toxin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2005_9 10.2210/rcsb_pdb/mom_2005_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MDT 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]] 2.3Å</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_1mdt| PDB=1mdt | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mdt OCA], [https://pdbe.org/1mdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mdt RCSB], [https://www.ebi.ac.uk/pdbsum/1mdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mdt 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 structure of toxic monomeric diphtheria toxin (DT) was determined at 2.3 A resolution by molecular replacement based on the domain structures in dimeric DT and refined to an R factor of 20.7%. The model consists of 2 monomers in the asymmetric unit (1,046 amino acid residues), including 2 bound adenylyl 3'-5' uridine 3' monophosphate molecules and 396 water molecules. The structures of the 3 domains are virtually identical in monomeric and dimeric DT; however, monomeric DT is compact and globular as compared to the "open" monomer within dimeric DT (Bennett MJ, Choe S, Eisenberg D, 1994b, Protein Sci 3:0000-0000). Detailed differences between monomeric and dimeric DT are described, particularly (1) changes in main-chain conformations of 8 residues acting as a hinge to "open" or "close" the receptor-binding (R) domain, and (2) a possible receptor-docking site, a beta-hairpin loop protruding from the R domain containing residues that bind the cell-surface DT receptor. Based on the monomeric and dimeric DT crystal structures we have determined and the solution studies of others, we present a 5-step structure-based mechanism of intoxication: (1) proteolysis of a disulfide-linked surface loop (residues 186-201) between the catalytic (C) and transmembrane (T) domains; (2) binding of a beta-hairpin loop protruding from the R domain to the DT receptor, leading to receptor-mediated endocytosis; (3) low pH-triggered open monomer formation and exposure of apolar surfaces in the T domain, which insert into the endosomal membrane; (4) translocation of the C domain into the cytosol; and (5) catalysis by the C domain of ADP-ribosylation of elongation factor 2. |
| | | | |
| - | '''THE REFINED STRUCTURE OF MONOMERIC DIPHTHERIA TOXIN AT 2.3 ANGSTROMS RESOLUTION'''
| + | Refined structure of monomeric diphtheria toxin at 2.3 A resolution.,Bennett MJ, Eisenberg D Protein Sci. 1994 Sep;3(9):1464-75. PMID:7833808<ref>PMID:7833808</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | The structure of toxic monomeric diphtheria toxin (DT) was determined at 2.3 A resolution by molecular replacement based on the domain structures in dimeric DT and refined to an R factor of 20.7%. The model consists of 2 monomers in the asymmetric unit (1,046 amino acid residues), including 2 bound adenylyl 3'-5' uridine 3' monophosphate molecules and 396 water molecules. The structures of the 3 domains are virtually identical in monomeric and dimeric DT; however, monomeric DT is compact and globular as compared to the "open" monomer within dimeric DT (Bennett MJ, Choe S, Eisenberg D, 1994b, Protein Sci 3:0000-0000). Detailed differences between monomeric and dimeric DT are described, particularly (1) changes in main-chain conformations of 8 residues acting as a hinge to "open" or "close" the receptor-binding (R) domain, and (2) a possible receptor-docking site, a beta-hairpin loop protruding from the R domain containing residues that bind the cell-surface DT receptor. Based on the monomeric and dimeric DT crystal structures we have determined and the solution studies of others, we present a 5-step structure-based mechanism of intoxication: (1) proteolysis of a disulfide-linked surface loop (residues 186-201) between the catalytic (C) and transmembrane (T) domains; (2) binding of a beta-hairpin loop protruding from the R domain to the DT receptor, leading to receptor-mediated endocytosis; (3) low pH-triggered open monomer formation and exposure of apolar surfaces in the T domain, which insert into the endosomal membrane; (4) translocation of the C domain into the cytosol; and (5) catalysis by the C domain of ADP-ribosylation of elongation factor 2.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1MDT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Corynephage_beta Corynephage beta]. The following page contains interesting information on the relation of 1MDT with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb69_1.html Cholera Toxin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MDT OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1mdt" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Refined structure of monomeric diphtheria toxin at 2.3 A resolution., Bennett MJ, Eisenberg D, Protein Sci. 1994 Sep;3(9):1464-75. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7833808 7833808]
| + | *[[Diphtheria toxin|Diphtheria toxin]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Cholera Toxin]] | | [[Category: Cholera Toxin]] |
| | [[Category: Corynephage beta]] | | [[Category: Corynephage beta]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Bennett, M J.]] | + | [[Category: RCSB PDB Molecule of the Month]] |
| - | [[Category: Eisenberg, D.]] | + | [[Category: Bennett MJ]] |
| - | [[Category: Toxin]] | + | [[Category: Eisenberg D]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:55:21 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 structure of toxic monomeric diphtheria toxin (DT) was determined at 2.3 A resolution by molecular replacement based on the domain structures in dimeric DT and refined to an R factor of 20.7%. The model consists of 2 monomers in the asymmetric unit (1,046 amino acid residues), including 2 bound adenylyl 3'-5' uridine 3' monophosphate molecules and 396 water molecules. The structures of the 3 domains are virtually identical in monomeric and dimeric DT; however, monomeric DT is compact and globular as compared to the "open" monomer within dimeric DT (Bennett MJ, Choe S, Eisenberg D, 1994b, Protein Sci 3:0000-0000). Detailed differences between monomeric and dimeric DT are described, particularly (1) changes in main-chain conformations of 8 residues acting as a hinge to "open" or "close" the receptor-binding (R) domain, and (2) a possible receptor-docking site, a beta-hairpin loop protruding from the R domain containing residues that bind the cell-surface DT receptor. Based on the monomeric and dimeric DT crystal structures we have determined and the solution studies of others, we present a 5-step structure-based mechanism of intoxication: (1) proteolysis of a disulfide-linked surface loop (residues 186-201) between the catalytic (C) and transmembrane (T) domains; (2) binding of a beta-hairpin loop protruding from the R domain to the DT receptor, leading to receptor-mediated endocytosis; (3) low pH-triggered open monomer formation and exposure of apolar surfaces in the T domain, which insert into the endosomal membrane; (4) translocation of the C domain into the cytosol; and (5) catalysis by the C domain of ADP-ribosylation of elongation factor 2.
Refined structure of monomeric diphtheria toxin at 2.3 A resolution.,Bennett MJ, Eisenberg D Protein Sci. 1994 Sep;3(9):1464-75. PMID:7833808[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, Eisenberg D. Refined structure of monomeric diphtheria toxin at 2.3 A resolution. Protein Sci. 1994 Sep;3(9):1464-75. PMID:7833808
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