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7y07

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Crystal structure of Ricin A chain bound with (S)-2-amino-N-(1-hydroxy-3-phenylpropan-2-yl)-4-oxo-3,4-dihydropteridine-7-carboxamide

Structural highlights

7y07 is a 1 chain structure with sequence from Ricinus communis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.25Å
Ligands:	,
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).

Publication Abstract from PubMed

Ricin toxin A-chain (RTA), a toxic protein from Ricinus communis, inactivates ribosomes to induce toxicity. The active site of RTA consists of two binding pockets. Many studies have focused on developing RTA inhibitors that can simultaneously bind to these critical pockets; however, almost all the inhibitors developed so far interact with only one pocket. In the present study, we discovered that pterin-7-carboxamides with aromatic l-amino acid pendants interacted with the active site of the enzyme in a 2-to-1 mode, where one inhibitor molecule bound to the primary pocket and the second one entered the secondary pocket in the active site of RTA. X-ray crystallographic analysis of inhibitor/RTA complexes revealed that the conformational changes of Tyr80 and Asn122 in RTA were critical for triggering the entry of inhibitor molecules into the secondary pocket of the RTA active site.

Conformational change in ricin toxin A-Chain: A critical factor for inhibitor binding to the secondary pocket.,Goto M, Higashi S, Ohba T, Kawata R, Nagatsu K, Suzuki S, Anslyn EV, Saito R Biochem Biophys Res Commun. 2022 Oct 30;627:1-4. doi: 10.1016/j.bbrc.2022.08.008. , Epub 2022 Aug 13. PMID:35998389^[1]

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

References

↑ Goto M, Higashi S, Ohba T, Kawata R, Nagatsu K, Suzuki S, Anslyn EV, Saito R. Conformational change in ricin toxin A-Chain: A critical factor for inhibitor binding to the secondary pocket. Biochem Biophys Res Commun. 2022 Oct 30;627:1-4. doi: 10.1016/j.bbrc.2022.08.008. , Epub 2022 Aug 13. PMID:35998389 doi:http://dx.doi.org/10.1016/j.bbrc.2022.08.008

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7y07"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7y07]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y07 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IFX:2-azanyl-4-oxidanylidene-N-[(2S)-1-oxidanyl-3-phenyl-propan-2-yl]-3H-pteridine-7-carboxamide'>IFX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.25&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IFX:2-azanyl-4-oxidanylidene-N-[(2S)-1-oxidanyl-3-phenyl-propan-2-yl]-3H-pteridine-7-carboxamide'>IFX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7y07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y07 OCA], [https://pdbe.org/7y07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y07 RCSB], [https://www.ebi.ac.uk/pdbsum/7y07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y07 ProSAT]</span></td></tr>
 </table>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7y07" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ricin 3D structures|Ricin 3D structures]]
 == References ==
 <references/>

7y07

From Proteopedia

Current revision

Crystal structure of Ricin A chain bound with (S)-2-amino-N-(1-hydroxy-3-phenylpropan-2-yl)-4-oxo-3,4-dihydropteridine-7-carboxamide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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