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==Structure of ricin A chain bound with benzyl-(2-(2-amino-4-oxo-3,4-dihydropteridine-7-carboxamido)ethyl)carbamate== | |||
<StructureSection load='4mx5' size='340' side='right' caption='[[4mx5]], [[Resolution|resolution]] 1.52Å' scene=''> | |||
{{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4mx5]] 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=4MX5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MX5 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5MX:BENZYL+(2-{[(2-AMINO-4-OXO-3,4-DIHYDROPTERIDIN-7-YL)CARBONYL]AMINO}ETHYL)CARBAMATE'>5MX</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rtc|1rtc]], [[1ift|1ift]], [[1br6|1br6]], [[3px8|3px8]], [[4hup|4hup]], [[4mx1|4mx1]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mx5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mx5 RCSB], [http://www.ebi.ac.uk/pdbsum/4mx5 PDBsum]</span></td></tr> | |||
</table> | |||
<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> | |||
== | ==See Also== | ||
*[[Ricin|Ricin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Castor bean]] | |||
[[Category: RRNA N-glycosylase]] | [[Category: RRNA N-glycosylase]] | ||
[[Category: Anslyn, E V | [[Category: Anslyn, E V]] | ||
[[Category: Gao, G | [[Category: Gao, G]] | ||
[[Category: Jasheway, K R | [[Category: Jasheway, K R]] | ||
[[Category: Manzano, L A | [[Category: Manzano, L A]] | ||
[[Category: Monzingo, A F | [[Category: Monzingo, A F]] | ||
[[Category: Pruet, J M | [[Category: Pruet, J M]] | ||
[[Category: Robertus, J D | [[Category: Robertus, J D]] | ||
[[Category: Saito, R | [[Category: Saito, R]] | ||
[[Category: Wiget, P A | [[Category: Wiget, P A]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 20:03, 21 December 2014
Structure of ricin A chain bound with benzyl-(2-(2-amino-4-oxo-3,4-dihydropteridine-7-carboxamido)ethyl)carbamateStructure of ricin A chain bound with benzyl-(2-(2-amino-4-oxo-3,4-dihydropteridine-7-carboxamido)ethyl)carbamate
Structural highlights
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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