caa a22 4500 475744330 CHVBK 20180406123508.0 cr unu---uuuuu 170329e20000501xx s 000 0 eng 10.1023/A:1007047413373 doi (NATIONALLICENCE)springer-10.1023/A:1007047413373 Molecular Modeling of the Interactions of Trichosanthin with Four Substrate Analogs [Elektronische Daten] [Yijun Gu, Weiyan Chen, Zongxiang Xia] Trichosanthin (TCS) is a ribosome-inactivating protein (RIP) that possesses N-glycosidase activity. It inactivates ribosomes and arrests protein synthesis by removing a specific adenine from 28S rRNA. A molecular dynamics simulated annealing method was applied to study the binding modes of TCS with substrate analogs, three oligonucleotides GAG, GAGA, and CGAGAG, based on the crystal structures of the stable complexes of TCS with NADPH and with the reaction product adenine. A water molecule proposed to be responsible for hydrolyzing the N-glycosidic bond was included in the model. All the oligoribonucleotides can dock into the active cleft of TCS without unfavorable contacts. The interaction energies between TCS and the three oligonucleotides were calculated. The interactions of TCS with NADH were also studied by a molecular dynamics simulated annealing method. The interaction energy between NADH and TCS was compared with that between NADPH and TCS, showing that the lack of 2′-phosphate group leads to an energy rise of 20 kcal/mol. Plenum Publishing Corporation, 2000 Trichosanthin nationallicence substrate analogues nationallicence molecular dynamics nationallicence simulated annealing nationallicence interaction energy nationallicence Gu Yijun State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, China aut Chen Weiyan State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, China aut Xia Zongxiang State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, China aut Journal of Protein Chemistry Kluwer Academic Publishers-Plenum Publishers 19/4(2000-05-01), 291-297 0277-8033 19:4<291 2000 19 10930 https://doi.org/10.1023/A:1007047413373 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007047413373 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gu Yijun State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, China aut NATIONALLICENCE 700 1- Chen Weiyan State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, China aut NATIONALLICENCE 700 1- Xia Zongxiang State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, China aut NATIONALLICENCE 773 0- Journal of Protein Chemistry Kluwer Academic Publishers-Plenum Publishers 19/4(2000-05-01), 291-297 0277-8033 19:4<291 2000 19 10930 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer