4esi: Difference between revisions

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<StructureSection load='4esi' size='340' side='right'caption='[[4esi]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
<StructureSection load='4esi' size='340' side='right'caption='[[4esi]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4esi]] 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=4ESI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ESI FirstGlance]. <br>
<table><tr><td colspan='2'>[[4esi]] 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=4ESI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ESI FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0RB:2-AMINO-4-OXO-N-(1H-1,2,3-TRIAZOL-5-YLMETHYL)-1,4-DIHYDROPTERIDINE-7-CARBOXAMIDE'>0RB</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]] 1.87&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rtc|1rtc]], [[1ift|1ift]], [[1br6|1br6]], [[1br5|1br5]], [[3px8|3px8]], [[3px9|3px9]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0RB:2-AMINO-4-OXO-N-(1H-1,2,3-TRIAZOL-5-YLMETHYL)-1,4-DIHYDROPTERIDINE-7-CARBOXAMIDE'>0RB</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] </span></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=4esi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4esi OCA], [https://pdbe.org/4esi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4esi RCSB], [https://www.ebi.ac.uk/pdbsum/4esi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4esi ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4esi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4esi OCA], [http://pdbe.org/4esi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4esi RCSB], [http://www.ebi.ac.uk/pdbsum/4esi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4esi ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/RICI_RICCO 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).  
[https://www.uniprot.org/uniprot/RICI_RICCO 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).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The optimization of a series of pterin amides for use as Ricin Toxin A (RTA) inhibitors is reported. Based upon crystallographic data of a previous furan-linked pterin, various expanded furans were synthesized, linked to the pterin and tested for inhibition. Concurrently, hetero-analogs of furan were explored, leading to the discovery of more potent triazol-linked pterins. Additionally, we discuss a dramatic improvement in the synthesis of these pterin amides via a dual role by diazabicycloundecene (DBU). This synthetic enhancement facilitates rapid diversification of the previously challenging pterin heterocycle, potentially aiding future medicinal research involving this structure.
 
Optimized 5-membered heterocycle-linked pterins for the inhibition of Ricin Toxin A.,Pruet JM, Saito R, Manzano LA, Jasheway KR, Wiget PA, Kamat I, Anslyn EV, Robertus JD ACS Med Chem Lett. 2012 Jul 12;3(7):588-591. Epub 2012 May 29. PMID:23050058<ref>PMID:23050058</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4esi" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Ricin|Ricin]]
*[[Ricin 3D structures|Ricin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Castor bean]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: RRNA N-glycosylase]]
[[Category: Ricinus communis]]
[[Category: Anslyn, E V]]
[[Category: Anslyn EV]]
[[Category: Jasheway, K R]]
[[Category: Jasheway KR]]
[[Category: Kamat, I]]
[[Category: Kamat I]]
[[Category: Manzano, L A]]
[[Category: Manzano LA]]
[[Category: Monzingo, A F]]
[[Category: Monzingo AF]]
[[Category: Pruet, J M]]
[[Category: Pruet JM]]
[[Category: Robertus, J D]]
[[Category: Robertus JD]]
[[Category: Ryoto, S]]
[[Category: Ryoto S]]
[[Category: Wiget, P A]]
[[Category: Wiget PA]]
[[Category: Hydrolase]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Hydrolase-inhibitor]]
[[Category: N-glycosidase]]
[[Category: Protein-ligand complex]]
[[Category: Pterin]]
[[Category: Ribosome inactivating protein]]
[[Category: Ricin]]
[[Category: Toxin]]

Latest revision as of 18:08, 14 March 2024

Structure of ricin A chain bound with N-((1H-1,2,3-triazol-4-yl)methyl-2-amino-4-oxo-3,4-dihydropteridine-7-carboxamideStructure of ricin A chain bound with N-((1H-1,2,3-triazol-4-yl)methyl-2-amino-4-oxo-3,4-dihydropteridine-7-carboxamide

Structural highlights

4esi 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 1.87Å
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).

See Also

4esi, resolution 1.87Å

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