The solution structure of a cytotoxic ribonuclease from the oocytes of Rana catesbeiana (bullfrog)

Chi Fon Chang, Chinpan Chen, Yi Cheng Chen, Kellie Hom, Rong Fong Huang, Tai-huang Huang

研究成果: 雜誌貢獻文章

24 引文 (Scopus)

摘要

RC-RNase is a pyrimidine-guanine sequence-specific ribonuclease and a lectin possessing potent cell cytotoxicity. It was isolated from the oocytes of Rana catesbeiana (bull frog). From analysis of an extensive set of 1H homonuclear 2D NMR spectra we have completed the resonance assignments. Determination of the three-dimensional structure was carried out with the program X-PLOR using a total of 951 restraints including 814 NMR-derived distances, 61 torsion angles, and 76 hydrogen bond restraints. In the resultant family of 15 best structures, selected from a total of 150 calculated structures, the root-mean-square deviation from the average structure for the backbone heavy-atoms involved in well-defined secondary structure is 0.48 Å, while that for all backbone heavy-atoms is 0.91 Å. The structure of RC-RNase consists of three α-helices and two triple-stranded anti-parallel β-sheets and folds in a kidney-shape, very similar to the X-ray crystal structure of a homologous protein, onconase isolated from Rana pipiens. We have also investigated the interaction between RC-RNase and two inhibitors, cytidylyl(2'→5')guanosine (2',5'-CpG) and 2'-deoxycytidylyl(3'→5')-2'-deoxyguanosine (3',5'-dCpdG). Based on the ligand-induced chemical shift changes in RC-RNase and the NOE cross-peaks between RC-RNase and the inhibitors, the key residues involved in protein-inhibitor interaction have been identified. The inhibitors were found to bind in a 'retro-binding' mode, with the guanine base bonded to the B1 subsite. The His103 residue was found to occupy the B state with the imidazole ring pointing away from the active site. The structure coordinates and the NMR restraints have been deposited in the Brookhaven Protein Data Bank (1bc4 and 1bc4mr, respectively).

原文英語
頁(從 - 到)231-244
頁數14
期刊Journal of Molecular Biology
283
發行號1
DOIs
出版狀態已發佈 - 1998 十月 16

指紋

Rana catesbeiana
Ribonucleases
Oocytes
Guanine
Rana pipiens
Proteins
Lectins
Anura
Hydrogen
Catalytic Domain
X-Rays
Databases
Ligands
Kidney

ASJC Scopus subject areas

  • Molecular Biology

引用此文

The solution structure of a cytotoxic ribonuclease from the oocytes of Rana catesbeiana (bullfrog). / Chang, Chi Fon; Chen, Chinpan; Chen, Yi Cheng; Hom, Kellie; Huang, Rong Fong; Huang, Tai-huang.

於: Journal of Molecular Biology, 卷 283, 編號 1, 16.10.1998, p. 231-244.

研究成果: 雜誌貢獻文章

Chang, Chi Fon ; Chen, Chinpan ; Chen, Yi Cheng ; Hom, Kellie ; Huang, Rong Fong ; Huang, Tai-huang. / The solution structure of a cytotoxic ribonuclease from the oocytes of Rana catesbeiana (bullfrog). 於: Journal of Molecular Biology. 1998 ; 卷 283, 編號 1. 頁 231-244.
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abstract = "RC-RNase is a pyrimidine-guanine sequence-specific ribonuclease and a lectin possessing potent cell cytotoxicity. It was isolated from the oocytes of Rana catesbeiana (bull frog). From analysis of an extensive set of 1H homonuclear 2D NMR spectra we have completed the resonance assignments. Determination of the three-dimensional structure was carried out with the program X-PLOR using a total of 951 restraints including 814 NMR-derived distances, 61 torsion angles, and 76 hydrogen bond restraints. In the resultant family of 15 best structures, selected from a total of 150 calculated structures, the root-mean-square deviation from the average structure for the backbone heavy-atoms involved in well-defined secondary structure is 0.48 {\AA}, while that for all backbone heavy-atoms is 0.91 {\AA}. The structure of RC-RNase consists of three α-helices and two triple-stranded anti-parallel β-sheets and folds in a kidney-shape, very similar to the X-ray crystal structure of a homologous protein, onconase isolated from Rana pipiens. We have also investigated the interaction between RC-RNase and two inhibitors, cytidylyl(2'→5')guanosine (2',5'-CpG) and 2'-deoxycytidylyl(3'→5')-2'-deoxyguanosine (3',5'-dCpdG). Based on the ligand-induced chemical shift changes in RC-RNase and the NOE cross-peaks between RC-RNase and the inhibitors, the key residues involved in protein-inhibitor interaction have been identified. The inhibitors were found to bind in a 'retro-binding' mode, with the guanine base bonded to the B1 subsite. The His103 residue was found to occupy the B state with the imidazole ring pointing away from the active site. The structure coordinates and the NMR restraints have been deposited in the Brookhaven Protein Data Bank (1bc4 and 1bc4mr, respectively).",
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AU - Huang, Rong Fong

AU - Huang, Tai-huang

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AB - RC-RNase is a pyrimidine-guanine sequence-specific ribonuclease and a lectin possessing potent cell cytotoxicity. It was isolated from the oocytes of Rana catesbeiana (bull frog). From analysis of an extensive set of 1H homonuclear 2D NMR spectra we have completed the resonance assignments. Determination of the three-dimensional structure was carried out with the program X-PLOR using a total of 951 restraints including 814 NMR-derived distances, 61 torsion angles, and 76 hydrogen bond restraints. In the resultant family of 15 best structures, selected from a total of 150 calculated structures, the root-mean-square deviation from the average structure for the backbone heavy-atoms involved in well-defined secondary structure is 0.48 Å, while that for all backbone heavy-atoms is 0.91 Å. The structure of RC-RNase consists of three α-helices and two triple-stranded anti-parallel β-sheets and folds in a kidney-shape, very similar to the X-ray crystal structure of a homologous protein, onconase isolated from Rana pipiens. We have also investigated the interaction between RC-RNase and two inhibitors, cytidylyl(2'→5')guanosine (2',5'-CpG) and 2'-deoxycytidylyl(3'→5')-2'-deoxyguanosine (3',5'-dCpdG). Based on the ligand-induced chemical shift changes in RC-RNase and the NOE cross-peaks between RC-RNase and the inhibitors, the key residues involved in protein-inhibitor interaction have been identified. The inhibitors were found to bind in a 'retro-binding' mode, with the guanine base bonded to the B1 subsite. The His103 residue was found to occupy the B state with the imidazole ring pointing away from the active site. The structure coordinates and the NMR restraints have been deposited in the Brookhaven Protein Data Bank (1bc4 and 1bc4mr, respectively).

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