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[[Image:1mdt.gif|left|200px]]


{{Structure
==THE REFINED STRUCTURE OF MONOMERIC DIPHTHERIA TOXIN AT 2.3 ANGSTROMS RESOLUTION==
|PDB= 1mdt |SIZE=350|CAPTION= <scene name='initialview01'>1mdt</scene>, resolution 2.3&Aring;
<StructureSection load='1mdt' size='340' side='right'caption='[[1mdt]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=APU:ADENYLYL-3'-5'-PHOSPHO-URIDINE-3'-MONOPHOSPHATE'>APU</scene>
<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>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
|GENE=  
<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>
}}
<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>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1mdt" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Diphtheria toxin|Diphtheria toxin]]
 
== References ==
==About this Structure==
<references/>
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].
__TOC__
 
</StructureSection>
==Reference==
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]
[[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: APU]]
[[Category: Eisenberg D]]
[[Category: toxin]]
 
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