1tox: Difference between revisions
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[[ | ==DIPHTHERIA TOXIN DIMER COMPLEXED WITH NAD== | ||
<StructureSection load='1tox' size='340' side='right' caption='[[1tox]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1tox]] is a 2 chain structure with 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=1TOX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TOX FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene><br> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)--diphthamide_ADP-ribosyltransferase NAD(+)--diphthamide ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.36 2.4.2.36] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tox OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1tox RCSB], [http://www.ebi.ac.uk/pdbsum/1tox PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Diphtheria toxin (DT), a 58 kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae, causes the disease diphtheria in humans by gaining entry into the cytoplasm of cells and inhibiting protein synthesis. Specifically, the catalytic (C) domain of DT transfers the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. In order to investigate how the C-domain of DT binds NAD and catalyzes the ADP-ribosylation of EF-2, the crystal structure of DT in complex with NAD has been determined to 2.3 A resolution. This is the first crystal structure of an ADP-ribosyltransferase (ADP-RT) enzyme in complex with NAD and suggests the features of the ADP-RT fold which are important for NAD binding. The conformation of NAD in the complex and the proximity of the Glu148 carboxylate group of the C-domain to the scissile, N-glycosidic bond of NAD suggest plausible modes of catalysis of the ADP-ribosylation reaction. Residues 39-46 of the active-site loop of the C-domain become disordered upon NAD binding, suggesting a potential role for this loop in the recognition of the ADP-ribose acceptor substrate, EF-2. The negatively charged phosphates and two ribose hydroxyls of NAD are not in direct contact with any atoms of the C-domain. Instead, they form an exposed surface which appears to be presented for recognition by EF-2. Structural alignments of the DT-NAD complex with the structures of other members of the ADP-RT family suggest how NAD may bind to these other enzymes. | |||
Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide.,Bell CE, Eisenberg D Biochemistry. 1996 Jan 30;35(4):1137-49. PMID:8573568<ref>PMID:8573568</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Corynephage beta]] | [[Category: Corynephage beta]] | ||
[[Category: Bell, C E.]] | [[Category: Bell, C E.]] | ||
Revision as of 09:49, 9 June 2014
DIPHTHERIA TOXIN DIMER COMPLEXED WITH NADDIPHTHERIA TOXIN DIMER COMPLEXED WITH NAD
Structural highlights
Publication Abstract from PubMedDiphtheria toxin (DT), a 58 kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae, causes the disease diphtheria in humans by gaining entry into the cytoplasm of cells and inhibiting protein synthesis. Specifically, the catalytic (C) domain of DT transfers the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. In order to investigate how the C-domain of DT binds NAD and catalyzes the ADP-ribosylation of EF-2, the crystal structure of DT in complex with NAD has been determined to 2.3 A resolution. This is the first crystal structure of an ADP-ribosyltransferase (ADP-RT) enzyme in complex with NAD and suggests the features of the ADP-RT fold which are important for NAD binding. The conformation of NAD in the complex and the proximity of the Glu148 carboxylate group of the C-domain to the scissile, N-glycosidic bond of NAD suggest plausible modes of catalysis of the ADP-ribosylation reaction. Residues 39-46 of the active-site loop of the C-domain become disordered upon NAD binding, suggesting a potential role for this loop in the recognition of the ADP-ribose acceptor substrate, EF-2. The negatively charged phosphates and two ribose hydroxyls of NAD are not in direct contact with any atoms of the C-domain. Instead, they form an exposed surface which appears to be presented for recognition by EF-2. Structural alignments of the DT-NAD complex with the structures of other members of the ADP-RT family suggest how NAD may bind to these other enzymes. Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide.,Bell CE, Eisenberg D Biochemistry. 1996 Jan 30;35(4):1137-49. PMID:8573568[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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