4MX5

Structure of ricin A chain bound with benzyl-(2-(2-amino-4-oxo-3,4-dihydropteridine-7-carboxamido)ethyl)carbamate

Summary for 4MX5

• Entry DOI: 10.2210/pdb4mx5/pdb
• Related: 1BR6 1IFT 1RTC 3PX8 4HUP 4MX1
• Descriptor: Ricin A chain, benzyl (2-{[(2-amino-4-oxo-3,4-dihydropteridin-7-yl)carbonyl]amino}ethyl)carbamate (3 entities in total)
• Functional Keywords: toxin, hydrolase, ribosome-inactivating protein, n-glycosidase, pterin, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Ricinus communis (Castor bean)
• Total number of polymer chains: 1
• Total formula weight: 30451.31

Authors

Jasheway, K.R.,Robertus, J.D.,Wiget, P.A.,Manzano, L.A.,Pruet, J.M.,Gao, G.,Saito, R.,Monzingo, A.F.,Anslyn, E.V. (deposition date: 2013-09-25, release date: 2014-01-15, Last modification date: 2023-09-20)

Primary citation

Wiget, P.A.,Manzano, L.A.,Pruet, J.M.,Gao, G.,Saito, R.,Monzingo, A.F.,Jasheway, K.R.,Robertus, J.D.,Anslyn, E.V.
Sulfur incorporation generally improves Ricin inhibition in pterin-appended glycine-phenylalanine dipeptide mimics.
Bioorg.Med.Chem.Lett., 23:6799-6804, 2013

PubMed Abstract: 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 μM), yet the analogous thioamide 7 recovered the lost activity and performed similarly to the parent inhibitor (IC50 = 29 μM). 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.

PubMed: 24432385

Experimental method

X-RAY DIFFRACTION (1.52 Å)