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3ej5

From Proteopedia

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Revision as of 07:19, 7 August 2019

complex of Ricin A chain and pyrimidine-based inhibitor

Structural highlights

3ej5 is a 1 chain structure with sequence from Castor bean. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	rRNA N-glycosylase, with EC number 3.2.2.22
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RICI_RICCO] Ricin is highly toxic to animal cells and to a lesser extent to plant cells. The A chain acts as a glycosidase that removes a specific adenine residue from an exposed loop of the 28S rRNA (A4324 in mammals), leading to rRNA breakage. As this loop is involved in elongation factor binding, modified ribosomes are catalytically inactive and unable to support protein synthesis. The A chain can inactivate a few thousand ribosomes per minute, faster than the cell can make new ones. Therefore a single A chain molecule can kill an animal cell. The B chain binds to beta-D-galactopyranoside moieties on cell surface glycoproteins and glycolipids and facilitates the entry into the cell of the A chain; B chains are also responsible for cell agglutination (Lectin activity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Ricin is a potent heterodimeric cytotoxin; the B chain binds eucaryotic cell surfaces aiding uptake and the A chain, RTA, reaches the cytoplasm where it enzymatically depurinates a key ribosomal adenine, inhibiting protein synthesis. Ricin is known to be an agent in bioterrorist repertoires and there is great interest in finding, or creating, efficacious inhibitors of the toxin as potential antidotes. We have previously identified two families of bicyclic RTA inhibitors, pterins and purines. Both classes have poor solubility which impairs inhibitor development. Here we report the use of 2-amino-4,6-dihydroxy-pyrimidines as RTA inhibitors. Unlike previously observed single ring inhibitor platforms, these displace Tyr 80 and bind deep in the RTA specificity pocket. These compounds are at least 10 times more soluble than pterin-based inhibitors and appear to be useful new class of ricin inhibitors.

The X-ray structure of ricin A chain with a novel inhibitor.,Bai Y, Monzingo AF, Robertus JD Arch Biochem Biophys. 2009 Mar 1;483(1):23-8. Epub 2008 Dec 30. PMID:19138659^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bai Y, Monzingo AF, Robertus JD. The X-ray structure of ricin A chain with a novel inhibitor. Arch Biochem Biophys. 2009 Mar 1;483(1):23-8. Epub 2008 Dec 30. PMID:19138659 doi:10.1016/j.abb.2008.12.013

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ej5"

@@ Line 1: / Line 1: @@
 ==complex of Ricin A chain and pyrimidine-based inhibitor==
-<StructureSection load='3ej5' size='340' side='right' caption='[[3ej5]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='3ej5' size='340' side='right'caption='[[3ej5]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3ej5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Castor_bean Castor bean]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EJ5 FirstGlance]. <br>
@@ Line 14: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ej/3ej5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ej/3ej5_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Castor bean]]
+[[Category: Large Structures]]
 [[Category: RRNA N-glycosylase]]
 [[Category: Bai, Y]]

3ej5

From Proteopedia

Revision as of 07:19, 7 August 2019

complex of Ricin A chain and pyrimidine-based inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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