1tox: Difference between revisions
New page: left|200px<br /><applet load="1tox" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tox, resolution 2.3Å" /> '''DIPHTHERIA TOXIN DIME... |
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[[Image:1tox.jpg|left|200px]]<br /><applet load="1tox" size=" | [[Image:1tox.jpg|left|200px]]<br /><applet load="1tox" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1tox, resolution 2.3Å" /> | caption="1tox, resolution 2.3Å" /> | ||
'''DIPHTHERIA TOXIN DIMER COMPLEXED WITH NAD'''<br /> | '''DIPHTHERIA TOXIN DIMER COMPLEXED WITH NAD'''<br /> | ||
==Overview== | ==Overview== | ||
Diphtheria toxin (DT), a 58 kDa protein secreted by lysogenic strains of | 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. | ||
==About this Structure== | ==About this Structure== | ||
1TOX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Corynephage_beta Corynephage beta] with NAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | 1TOX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Corynephage_beta Corynephage beta] with <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TOX OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: NAD(+)--diphthamide ADP-ribosyltransferase]] | [[Category: NAD(+)--diphthamide ADP-ribosyltransferase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bell, C | [[Category: Bell, C E.]] | ||
[[Category: Eisenberg, D.]] | [[Category: Eisenberg, D.]] | ||
[[Category: NAD]] | [[Category: NAD]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:15:51 2008'' | ||
Revision as of 16:15, 21 February 2008
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DIPHTHERIA TOXIN DIMER COMPLEXED WITH NAD
OverviewOverview
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.
About this StructureAbout this Structure
1TOX is a Single protein structure of sequence from Corynephage beta with as ligand. Active as NAD(+)--diphthamide ADP-ribosyltransferase, with EC number 2.4.2.36 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide., Bell CE, Eisenberg D, Biochemistry. 1996 Jan 30;35(4):1137-49. PMID:8573568
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