4ESI

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

Summary for 4ESI

• Entry DOI: 10.2210/pdb4esi/pdb
• Related: 1BR5 1BR6 1IFT 1RTC 3PX8 3PX9
• Descriptor: Ricin, 2-amino-4-oxo-N-(1H-1,2,3-triazol-5-ylmethyl)-1,4-dihydropteridine-7-carboxamide (3 entities in total)
• Functional Keywords: ricin, toxin, protein-ligand complex, hydrolase, ribosome inactivating protein, n-glycosidase, pterin, hydrolase-inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Ricinus communis (Castor bean)
• Total number of polymer chains: 1
• Total formula weight: 30224.00

Authors

Jasheway, K.R.,Pruet, J.M.,Ryoto, S.,Manzano, L.A.,Wiget, P.A.,Kamat, I.,Anslyn, E.V.,Monzingo, A.F.,Robertus, J.D. (deposition date: 2012-04-23, release date: 2012-10-31, Last modification date: 2023-09-13)

Primary citation

Pruet, J.M.,Saito, R.,Manzano, L.A.,Jasheway, K.R.,Wiget, P.A.,Kamat, I.,Anslyn, E.V.,Robertus, J.D.
Optimized 5-membered heterocycle-linked pterins for the inhibition of Ricin Toxin A.
ACS Med Chem Lett, 3:588-591, 2012

PubMed Abstract: 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.

PubMed: 23050058
DOI: 10.1021/ml300099t

Experimental method

X-RAY DIFFRACTION (1.87 Å)