title: Simulation analysis of formycin 5'-monophosphate analog substrates in the ricin A-chain active site.
abstract: 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.
authors.affiliation: Department of Cell Biology and Biochemistry, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Olson
authors.forename: J P
authors.initials: JP
authors.lastname: Scovill
authors.forename: D C
authors.initials: DC
authors.lastname: Hack
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D005573:Formycins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D012265:Ribonucleotides / Q000737:chemistry* / Q000378:metabolism; D012276:Ricin / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D005573:Formycins; D012265:Ribonucleotides; C021683:formycin 5'-phosphate; D012276:Ricin