4HUP

Structure of ricin A chain bound with N-(N-(pterin-7-yl)carbonylglycyl)-L-phenylalanyl)-L-phenylalanine

Summary for 4HUP

• Entry DOI: 10.2210/pdb4hup/pdb
• Related: 1BR6 1IFT 1PX8 1RTC 4ESI 4HV3 4HV7 4huo
• Descriptor: Ricin, (2S)-2-[[(2S)-2-[2-[(2-azanyl-4-oxidanylidene-1H-pteridin-7-yl)carbonylamino]ethanoylamino]-3-phenyl-propanoyl]amino]-3-phenyl-propanoic acid, SULFATE ION, ... (5 entities in total)
• Functional Keywords: ricin, protein-ligand complex, pterin, hydrolase-hydrolase inhibitor complex, toxin, hydrolase, ribosome-inactivating protein, n-glycosidase, hydrolase/hydrolase inhibitor
• Biological source: Ricinus communis (Castor bean)
• Total number of polymer chains: 1
• Total formula weight: 30895.55

Authors

Jasheway, K.R.,Monzingo, A.F.,Saito, R.,Pruet, J.M.,Manzano, L.A.,Wiget, P.A.,Anslyn, E.V.,Robertus, J.D. (deposition date: 2012-11-02, release date: 2012-12-26, Last modification date: 2023-09-20)

Primary citation

Saito, R.,Pruet, J.M.,Manzano, L.A.,Jasheway, K.,Monzingo, A.F.,Wiget, P.A.,Kamat, I.,Anslyn, E.V.,Robertus, J.D.
Peptide-conjugated pterins as inhibitors of ricin toxin A.
J.Med.Chem., 56:320-329, 2013

PubMed Abstract: Several 7-peptide-substituted pterins were synthesized and tested as competitive active-site inhibitors of ricin toxin A (RTA). Focus began on dipeptide conjugates, and these results further guided the construction of several tripeptide conjugates. The binding of these compounds to RTA was studied via a luminescence-based kinetic assay, as well as through X-ray crystallography. Despite the relatively polar, solvent exposed active site, several hydrophobic interactions, most commonly π-interactions not predicted by modeling programs, were identified in all of the best-performing inhibitors. Nearly all of these compounds provide IC₅₀ values in the low micromolar range.

PubMed: 23214944
DOI: 10.1021/jm3016393

Experimental method

X-RAY DIFFRACTION (1.699 Å)