ISSN:
1573-4951
Keywords:
Ricin
;
N-glycosidase
;
Enzyme-ligand complex
;
Molecular dynamics
;
Structural interactions
;
Binding free energies
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Summary Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis. Molecular-dynamics simulation methods are used to analyze the structural interactions and thermodynamics that govern the binding of formycin 5′-monophosphate (FMP) and several of its analogs to the active site of ricin A-chain. Simulations are carried out initiated from the X-ray crystal structure of the ricin-FMP complex with the ligand modeled as a dianion, monoanion and zwitterion. Relative changes in binding free energies are estimated for FMP analogs constructed from amino substitutions at the 2- and 2′-positions, and from hydroxyl substitution at the 2′-position.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00124454
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