4mx1: Difference between revisions
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The entry | ==Structure of ricin A chain bound with 2-amino-4-oxo-N-(2-(3-phenylureido)ethyl)-3,4-dihydropteridine-7-carboxamide== | ||
<StructureSection load='4mx1' size='340' side='right'caption='[[4mx1]], [[Resolution|resolution]] 1.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4mx1]] 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=4MX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MX1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MX:2-AMINO-4-OXO-N-{2-[(PHENYLCARBAMOYL)AMINO]ETHYL}-3,4-DIHYDROPTERIDINE-7-CARBOXAMIDE'>1MX</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</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=4mx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mx1 OCA], [https://pdbe.org/4mx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mx1 RCSB], [https://www.ebi.ac.uk/pdbsum/4mx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mx1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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 == | |||
Several 7-aminoamido-pterins were synthesized to evaluate the electronic and biochemical subtleties observed in the 'linker space' when N-{N-(pterin-7-yl)carbonylglycyl}-l-phenylalanine 1 was bound to the active site of RTA. The gylcine-phenylalanine dipeptide analogs included both amides and thioamides. Decarboxy gly-phe analog 2 showed a 6.4-fold decrease in potency (IC50 = 128 muM), yet the analogous thioamide 7 recovered the lost activity and performed similarly to the parent inhibitor (IC50 = 29 muM). Thiourea 12 exhibited an IC50 nearly six times lower than the oxo analog 13. All inhibitors showed the pterin head-group firmly bound in their X-ray structures yet the pendants were not fully resolved suggesting that all pendants are not firmly bound in the RTA linker space. Calculated log P values do not correlate to the increase in bioactivity suggesting other factors dominate. | |||
Sulfur incorporation generally improves Ricin inhibition in pterin-appended glycine-phenylalanine dipeptide mimics.,Wiget PA, Manzano LA, Pruet JM, Gao G, Saito R, Monzingo AF, Jasheway KR, Robertus JD, Anslyn EV Bioorg Med Chem Lett. 2013 Dec 15;23(24):6799-804. PMID:24432385<ref>PMID:24432385</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4mx1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ricin 3D structures|Ricin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Ricinus communis]] | |||
[[Category: Anslyn EV]] | |||
[[Category: Gao G]] | |||
[[Category: Jasheway KR]] | |||
[[Category: Manzano LA]] | |||
[[Category: Monzingo AF]] | |||
[[Category: Pruet JM]] | |||
[[Category: Robertus JD]] | |||
[[Category: Saito R]] | |||
[[Category: Wiget PA]] | |||
Latest revision as of 19:44, 20 September 2023
Structure of ricin A chain bound with 2-amino-4-oxo-N-(2-(3-phenylureido)ethyl)-3,4-dihydropteridine-7-carboxamideStructure of ricin A chain bound with 2-amino-4-oxo-N-(2-(3-phenylureido)ethyl)-3,4-dihydropteridine-7-carboxamide
Structural highlights
FunctionRICI_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 PubMedSeveral 7-aminoamido-pterins were synthesized to evaluate the electronic and biochemical subtleties observed in the 'linker space' when N-{N-(pterin-7-yl)carbonylglycyl}-l-phenylalanine 1 was bound to the active site of RTA. The gylcine-phenylalanine dipeptide analogs included both amides and thioamides. Decarboxy gly-phe analog 2 showed a 6.4-fold decrease in potency (IC50 = 128 muM), yet the analogous thioamide 7 recovered the lost activity and performed similarly to the parent inhibitor (IC50 = 29 muM). Thiourea 12 exhibited an IC50 nearly six times lower than the oxo analog 13. All inhibitors showed the pterin head-group firmly bound in their X-ray structures yet the pendants were not fully resolved suggesting that all pendants are not firmly bound in the RTA linker space. Calculated log P values do not correlate to the increase in bioactivity suggesting other factors dominate. Sulfur incorporation generally improves Ricin inhibition in pterin-appended glycine-phenylalanine dipeptide mimics.,Wiget PA, Manzano LA, Pruet JM, Gao G, Saito R, Monzingo AF, Jasheway KR, Robertus JD, Anslyn EV Bioorg Med Chem Lett. 2013 Dec 15;23(24):6799-804. PMID:24432385[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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