The Experts below are selected from a list of 3531 Experts worldwide ranked by ideXlab platform
Hai Pang - One of the best experts on this subject based on the ideXlab platform.
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characterization of the heptad repeat regions hr1 and hr2 and design of a fusion core structure model of the spike protein from severe acute respiratory syndrome sars coronaVirus
Biochemistry, 2004Co-Authors: Jieqing Zhu, Zhiyong Lou, Yiwei Liu, Fang Yuan, Yueyong Liu, David K Cole, Lan Qin, Zhihong Bai, John I Bell, Hai PangAbstract:Severe acute respiratory syndrome coronaVirus (SARS-CoV) is a newly Emergent Virus responsible for a worldwide epidemic in 2003. The coronaVirus spike proteins belong to class I fusion proteins, and are characterized by the existence of two heptad repeat (HR) regions, HR1 and HR2. The HR1 region in coronaViruses is predicted to be considerably longer than that in other type I Virus fusion proteins. Therefore the exact binding sequence to HR2 from the HR1 is not clear. In this study, we defined the region of HR1 that binds to HR2 by a series of biochemical and biophysical measures. Subsequently the defined HR1 (902−952) and HR2 (1145−1184) chains, which are different from previously defined binding regions, were linked together by a flexible linker to form a single-chain construct, 2-Helix. This protein was expressed in Escherichia coli and forms a typical six-helix coiled coil bundle. Highly conserved HR regions between mouse hepatitis Virus (MHV) and SARS-CoV spike proteins suggest a similar three-dimensional structure for the two fusion cores. Here, we constructed a homology model for SARS coronaVirus fusion core based on our biochemical analysis and determined the MHV fusion core structure. We also propose an important target site for fusion inhibitor design and several strategies, which have been successfully used in fusion inhibitor design for human immunodeficiency Virus (HIV), for the treatment of SARS infection.
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crystal structure of severe acute respiratory syndrome coronaVirus spike protein fusion core
Journal of Biological Chemistry, 2004Co-Authors: Yanhui Xu, Zhiyong Lou, Hai Pang, Po Tien, George F. Gao, Yiwei Liu, Zihe RaoAbstract:Severe acute respiratory syndrome coronaVirus is a newly Emergent Virus responsible for a recent outbreak of an atypical pneumonia. The coronaVirus spike protein, an enveloped glycoprotein essential for viral entry, belongs to the class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions are understood to form a fusion-active conformation similar to those of other typical viral fusion proteins. This hairpin structure likely juxtaposes the viral and cellular membranes, thus facilitating membrane fusion and subsequent viral entry. The fusion core protein of severe acute respiratory syndrome coronaVirus spike protein was crystallized, and the structure was determined at 2.8 A of resolution. The fusion core is a six-helix bundle with three HR2 helices packed against the hydrophobic grooves on the surface of central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. This structure shares significant similarity with the fusion core structure of mouse hepatitis Virus spike protein and other viral fusion proteins, suggesting a conserved mechanism of membrane fusion. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation, which have been successfully used in human immunodeficiency Virus 1 inhibitor development, may be applicable to the inhibition of severe acute respiratory syndrome coronaVirus on the basis of structural information provided here. The relatively deep grooves on the surface of the central coiled coil will be a good target site for the design of viral fusion inhibitors.
Zihe Rao - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of severe acute respiratory syndrome coronaVirus spike protein fusion core
Journal of Biological Chemistry, 2004Co-Authors: Yanhui Xu, Zhiyong Lou, Hai Pang, Po Tien, George F. Gao, Yiwei Liu, Zihe RaoAbstract:Severe acute respiratory syndrome coronaVirus is a newly Emergent Virus responsible for a recent outbreak of an atypical pneumonia. The coronaVirus spike protein, an enveloped glycoprotein essential for viral entry, belongs to the class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions are understood to form a fusion-active conformation similar to those of other typical viral fusion proteins. This hairpin structure likely juxtaposes the viral and cellular membranes, thus facilitating membrane fusion and subsequent viral entry. The fusion core protein of severe acute respiratory syndrome coronaVirus spike protein was crystallized, and the structure was determined at 2.8 A of resolution. The fusion core is a six-helix bundle with three HR2 helices packed against the hydrophobic grooves on the surface of central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. This structure shares significant similarity with the fusion core structure of mouse hepatitis Virus spike protein and other viral fusion proteins, suggesting a conserved mechanism of membrane fusion. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation, which have been successfully used in human immunodeficiency Virus 1 inhibitor development, may be applicable to the inhibition of severe acute respiratory syndrome coronaVirus on the basis of structural information provided here. The relatively deep grooves on the surface of the central coiled coil will be a good target site for the design of viral fusion inhibitors.
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biochemical and biophysical analysis of heptad repeat regions from the fusion protein of menangle Virus a newly Emergent paramyxoVirus
Archives of Virology, 2003Co-Authors: Jiawu Zhu, Po Tien, Zihe Rao, C W H Zhang, George F. GaoAbstract:expression system. The GST-removed purified 2-Helix protein could form a stable trimer in vitro judging by gel-filtration and chemical cross-linking. CD spectra showed that the 2-Helix protein had a high percentage of α-helix and was very thermo-stable. Crystals of the 2-Helix protein preparations have been obtained in many conditions with hanging-drop diffusion method. These results indicated that Menangle Virus has the common features of the fusion protein for other paramyxoViruses and should adopt a similar fusion mechanism to other members. As the HR regions of Menangle Virus F protein could form stable six-helix bundle coiled coil structure, they should be used as drug target for the design of fusion inhibitors, as successfully used for other parmyxoViruses. This is especially relevant to such a newly Emergent Virus with zoonotic potentials.
Zhiyong Lou - One of the best experts on this subject based on the ideXlab platform.
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characterization of the heptad repeat regions hr1 and hr2 and design of a fusion core structure model of the spike protein from severe acute respiratory syndrome sars coronaVirus
Biochemistry, 2004Co-Authors: Jieqing Zhu, Zhiyong Lou, Yiwei Liu, Fang Yuan, Yueyong Liu, David K Cole, Lan Qin, Zhihong Bai, John I Bell, Hai PangAbstract:Severe acute respiratory syndrome coronaVirus (SARS-CoV) is a newly Emergent Virus responsible for a worldwide epidemic in 2003. The coronaVirus spike proteins belong to class I fusion proteins, and are characterized by the existence of two heptad repeat (HR) regions, HR1 and HR2. The HR1 region in coronaViruses is predicted to be considerably longer than that in other type I Virus fusion proteins. Therefore the exact binding sequence to HR2 from the HR1 is not clear. In this study, we defined the region of HR1 that binds to HR2 by a series of biochemical and biophysical measures. Subsequently the defined HR1 (902−952) and HR2 (1145−1184) chains, which are different from previously defined binding regions, were linked together by a flexible linker to form a single-chain construct, 2-Helix. This protein was expressed in Escherichia coli and forms a typical six-helix coiled coil bundle. Highly conserved HR regions between mouse hepatitis Virus (MHV) and SARS-CoV spike proteins suggest a similar three-dimensional structure for the two fusion cores. Here, we constructed a homology model for SARS coronaVirus fusion core based on our biochemical analysis and determined the MHV fusion core structure. We also propose an important target site for fusion inhibitor design and several strategies, which have been successfully used in fusion inhibitor design for human immunodeficiency Virus (HIV), for the treatment of SARS infection.
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crystal structure of severe acute respiratory syndrome coronaVirus spike protein fusion core
Journal of Biological Chemistry, 2004Co-Authors: Yanhui Xu, Zhiyong Lou, Hai Pang, Po Tien, George F. Gao, Yiwei Liu, Zihe RaoAbstract:Severe acute respiratory syndrome coronaVirus is a newly Emergent Virus responsible for a recent outbreak of an atypical pneumonia. The coronaVirus spike protein, an enveloped glycoprotein essential for viral entry, belongs to the class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions are understood to form a fusion-active conformation similar to those of other typical viral fusion proteins. This hairpin structure likely juxtaposes the viral and cellular membranes, thus facilitating membrane fusion and subsequent viral entry. The fusion core protein of severe acute respiratory syndrome coronaVirus spike protein was crystallized, and the structure was determined at 2.8 A of resolution. The fusion core is a six-helix bundle with three HR2 helices packed against the hydrophobic grooves on the surface of central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. This structure shares significant similarity with the fusion core structure of mouse hepatitis Virus spike protein and other viral fusion proteins, suggesting a conserved mechanism of membrane fusion. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation, which have been successfully used in human immunodeficiency Virus 1 inhibitor development, may be applicable to the inhibition of severe acute respiratory syndrome coronaVirus on the basis of structural information provided here. The relatively deep grooves on the surface of the central coiled coil will be a good target site for the design of viral fusion inhibitors.
Yiwei Liu - One of the best experts on this subject based on the ideXlab platform.
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characterization of the heptad repeat regions hr1 and hr2 and design of a fusion core structure model of the spike protein from severe acute respiratory syndrome sars coronaVirus
Biochemistry, 2004Co-Authors: Jieqing Zhu, Zhiyong Lou, Yiwei Liu, Fang Yuan, Yueyong Liu, David K Cole, Lan Qin, Zhihong Bai, John I Bell, Hai PangAbstract:Severe acute respiratory syndrome coronaVirus (SARS-CoV) is a newly Emergent Virus responsible for a worldwide epidemic in 2003. The coronaVirus spike proteins belong to class I fusion proteins, and are characterized by the existence of two heptad repeat (HR) regions, HR1 and HR2. The HR1 region in coronaViruses is predicted to be considerably longer than that in other type I Virus fusion proteins. Therefore the exact binding sequence to HR2 from the HR1 is not clear. In this study, we defined the region of HR1 that binds to HR2 by a series of biochemical and biophysical measures. Subsequently the defined HR1 (902−952) and HR2 (1145−1184) chains, which are different from previously defined binding regions, were linked together by a flexible linker to form a single-chain construct, 2-Helix. This protein was expressed in Escherichia coli and forms a typical six-helix coiled coil bundle. Highly conserved HR regions between mouse hepatitis Virus (MHV) and SARS-CoV spike proteins suggest a similar three-dimensional structure for the two fusion cores. Here, we constructed a homology model for SARS coronaVirus fusion core based on our biochemical analysis and determined the MHV fusion core structure. We also propose an important target site for fusion inhibitor design and several strategies, which have been successfully used in fusion inhibitor design for human immunodeficiency Virus (HIV), for the treatment of SARS infection.
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crystal structure of severe acute respiratory syndrome coronaVirus spike protein fusion core
Journal of Biological Chemistry, 2004Co-Authors: Yanhui Xu, Zhiyong Lou, Hai Pang, Po Tien, George F. Gao, Yiwei Liu, Zihe RaoAbstract:Severe acute respiratory syndrome coronaVirus is a newly Emergent Virus responsible for a recent outbreak of an atypical pneumonia. The coronaVirus spike protein, an enveloped glycoprotein essential for viral entry, belongs to the class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions are understood to form a fusion-active conformation similar to those of other typical viral fusion proteins. This hairpin structure likely juxtaposes the viral and cellular membranes, thus facilitating membrane fusion and subsequent viral entry. The fusion core protein of severe acute respiratory syndrome coronaVirus spike protein was crystallized, and the structure was determined at 2.8 A of resolution. The fusion core is a six-helix bundle with three HR2 helices packed against the hydrophobic grooves on the surface of central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. This structure shares significant similarity with the fusion core structure of mouse hepatitis Virus spike protein and other viral fusion proteins, suggesting a conserved mechanism of membrane fusion. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation, which have been successfully used in human immunodeficiency Virus 1 inhibitor development, may be applicable to the inhibition of severe acute respiratory syndrome coronaVirus on the basis of structural information provided here. The relatively deep grooves on the surface of the central coiled coil will be a good target site for the design of viral fusion inhibitors.
George F. Gao - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of severe acute respiratory syndrome coronaVirus spike protein fusion core
Journal of Biological Chemistry, 2004Co-Authors: Yanhui Xu, Zhiyong Lou, Hai Pang, Po Tien, George F. Gao, Yiwei Liu, Zihe RaoAbstract:Severe acute respiratory syndrome coronaVirus is a newly Emergent Virus responsible for a recent outbreak of an atypical pneumonia. The coronaVirus spike protein, an enveloped glycoprotein essential for viral entry, belongs to the class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions are understood to form a fusion-active conformation similar to those of other typical viral fusion proteins. This hairpin structure likely juxtaposes the viral and cellular membranes, thus facilitating membrane fusion and subsequent viral entry. The fusion core protein of severe acute respiratory syndrome coronaVirus spike protein was crystallized, and the structure was determined at 2.8 A of resolution. The fusion core is a six-helix bundle with three HR2 helices packed against the hydrophobic grooves on the surface of central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. This structure shares significant similarity with the fusion core structure of mouse hepatitis Virus spike protein and other viral fusion proteins, suggesting a conserved mechanism of membrane fusion. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation, which have been successfully used in human immunodeficiency Virus 1 inhibitor development, may be applicable to the inhibition of severe acute respiratory syndrome coronaVirus on the basis of structural information provided here. The relatively deep grooves on the surface of the central coiled coil will be a good target site for the design of viral fusion inhibitors.
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biochemical and biophysical analysis of heptad repeat regions from the fusion protein of menangle Virus a newly Emergent paramyxoVirus
Archives of Virology, 2003Co-Authors: Jiawu Zhu, Po Tien, Zihe Rao, C W H Zhang, George F. GaoAbstract:expression system. The GST-removed purified 2-Helix protein could form a stable trimer in vitro judging by gel-filtration and chemical cross-linking. CD spectra showed that the 2-Helix protein had a high percentage of α-helix and was very thermo-stable. Crystals of the 2-Helix protein preparations have been obtained in many conditions with hanging-drop diffusion method. These results indicated that Menangle Virus has the common features of the fusion protein for other paramyxoViruses and should adopt a similar fusion mechanism to other members. As the HR regions of Menangle Virus F protein could form stable six-helix bundle coiled coil structure, they should be used as drug target for the design of fusion inhibitors, as successfully used for other parmyxoViruses. This is especially relevant to such a newly Emergent Virus with zoonotic potentials.