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Simulation analysis of formycin 5′-monophosphate analog substrates in the ricin A-chain active site

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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.

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Authors and Affiliations

  1. Department of Cell Biology and Biochemistry, U.S. Army Medical Research Institute of Infectious Diseases, 21702-5011, Frederick, MD, U.S.A.

    Mark A. Olson, John P. Scovill & Dallas C. Hack

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  1. Mark A. Olson
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  2. John P. Scovill
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  3. Dallas C. Hack
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Olson, M.A., Scovill, J.P. & Hack, D.C. Simulation analysis of formycin 5′-monophosphate analog substrates in the ricin A-chain active site. J Computer-Aided Mol Des 9, 226–236 (1995). https://doi.org/10.1007/BF00124454

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  • DOI: https://doi.org/10.1007/BF00124454

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