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ABSTRACT: Recent outbreak of H1N1 virus worldwide has caused 16 226 deaths in over 213 countries and districts. Binding between the virus and the receptor on the host cell surface is the key initial event for the infection, which results in the fusion of viral host cell membrane. Hemagglutinin (HA) is the viral protein that mediates the receptor binding and membrane fusion. The receptor binding sites (RBSs) are located at the membrane-distal part of each subunit of the HA trimer and are formed by three secondary structure elements, 190 helix (residues 190 to 198), 130 loop (residues 135 to 138), and 220 loop (residues 221 to 228). HA1 with 327 amino acid sequences in length was collected from 1221 H1N1 viruses between 1918 and 2009, and bioinformatic studies were carried out through sequence comparison, entropy calculation for each amino acid residue, and 3D structure modeling. The results showed that the RBSs of different viruses with different hosts have different entropies, and the RBSs in HA1 with different hosts have different favorite amino acid sequences. The 3D modeling indicates the subtly conformation changes in the 190 helix region between different HA1s in H1N1. This study explores new characters of the RBS structure in different HA1s, and provides new information for the further investigation of the infection mechanism.
Hereditas (Beijing) 07/2010; 32(7):701-11.
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ABSTRACT: Whooping cough (pertussis) caused by B. pertussis (B.p) is still serious public health threat. B. parapertussis (B.pp), closely related to B.p, also causes whooping cough. The incidence of B.pp infections has been increasing over the last decades, partly because pertussis vaccines have low efficiency against B.pp infections. Moreover, because the majority of pertussis patients are infants, common antimicrobial agents producing serious adverse reactions in infants are not fully satisfactory. Therefore, we try to identify potential vaccine candidates and alternative drug targets against both B.p and B.pp. This preliminary work integrates several different kinds of data from in silico analysis, comparative genomic hybridization, global transcriptional profiling, and protein-protein interaction (PPI) network to screen potential vaccine candidates and drug targets against the two species. Finally, 191 potential crossprotective vaccine candidates are identified. They have high transcriptional levels in both species, or are associated with virulence and pathogenesis. Moreover, these proteins are not only potentially surface-exposed in the bacteria, but also well conserved among the 165 B.p and B.pp strains. Among them, 22 candidates with high essentiality in the two PPI networks of B.p and B.pp are regarded as suitable drug targets against the two species. We just selected Bordetella as an example to develop a rapid and reliable approach for screening alternative drug targets that associated with novel protein pathways, complexes, and cellular functions against these antibiotic-resistant pathogens. Further researches focusing on the 191 vaccine candidates could accelerate the development of more effective vaccines and drug therapy against B.p and B.pp infection.
Omics: a journal of integrative biology 10/2008; 12(3):161-9. · 2.29 Impact Factor
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Qing-Bo Yu,
Guang Li,
Guan Wang,
Jing-Chun Sun,
Peng-Cheng Wang,
Chen Wang,
Hua-Ling Mi,
Wei-Min Ma,
Jian Cui,
Yong-Lan Cui,
Kang Chong,
Yi-Xue Li,
Yu-Hua Li,
Zhongming Zhao, Tie-Liu Shi,
Zhong-Nan Yang
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ABSTRACT: Chloroplast is a typical plant cell organelle where photosynthesis takes place. In this study, a total of 1,808 chloroplast core proteins in Arabidopsis thaliana were reliably identified by combining the results of previously published studies and our own predictions. We then constructed a chloroplast protein interaction network primarily based on these core protein interactions. The network had 22,925 protein interaction pairs which involved 2,214 proteins. A total of 160 previously uncharacterized proteins were annotated in this network. The subunits of the photosynthetic complexes were modularized, and the functional relationships among photosystem I (PSI), photosystem II (PSII), light harvesting complex of photosystem I (LHC I) and light harvesting complex of photosystem I (LHC II) could be deduced from the predicted protein interactions in this network. We further confirmed an interaction between an unknown protein AT1G52220 and a photosynthetic subunit PSI-D2 by yeast two-hybrid analysis. Our chloroplast protein interaction network should be useful for functional mining of photosynthetic proteins and investigation of chloroplast-related functions at the systems biology level in Arabidopsis.
Cell Research 10/2008; 18(10):1007-19. · 8.19 Impact Factor
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ABSTRACT: Protein-protein interactions play a central role in numerous processes in cell and are one of the main research fields in current functional proteomics. The increase of finished genomic sequences has greatly stimulated the progress for detecting the functions of the genes and their encoded proteins. As complementary ways to the high through-put experimental methods, various methods of bioinformatics have been developed for the study of the protein-protein interaction. These methods range from the sequence homology-based to the genomic-context based. Recently, it tends to integrate the data from different methods to build the protein-protein interaction network, and to predict the protein function from the analysis of the network structure. Efforts are ongoing to improve these methods and to search for novel aspects in genomes that could be exploited for function prediction. This review highlights the recent advances of the bioinformatics methods in protein-protein interaction researches. In the end, the application of the protein-protein interaction has also been discussed.
Current Protein and Peptide Science 11/2005; 6(5):443-9. · 2.89 Impact Factor
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ABSTRACT: Single nucleotide polymorphism (SNP) is the most common type of genetic variant in human genome. Haplotype, defined as a specific set of alleles observed on a single chromosome, or a part of a chromosome,has been an integral part of human genetics for decades. The goal of the international HapMap project is to determine the common patterns of DNA sequence variation and find the Tag SNPs representing all SNPs in the human genome. Some studies demonstrated that the analyses of haplotype defined by the grouping and interaction of several variants rather than any individual SNP correlated with complex phenotypes. Here, we describe the definitions of SNPs, genotype, haplotype and some information of the HapMap project. In this review, we summarize the current three haplotype-inference methods, including Clark' method, EM algorithm and Byes approach, and the different defining methods for haplotype block, as well as the methods for choosing tag SNPs and association studies of complex diseases using haplotype. The major public SNP databases and applications of SNPs and haplotype in common complex diseases and drug response are also introduced in the paper.
Acta Genetica Sinica 09/2005; 32(8):879-89.
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Wei Lu,
Xiao-Dong Wu,
Mu De Shi,
Rui Fu Yang,
You Yu He,
Chao Bian, Tie Liu Shi,
Sheng Yang,
Xue-Liang Zhu,
Wei-Hong Jiang, [......],
Yong Yong Ji,
Ying Lin,
Guo-Mei Lin,
Lin Tian,
Jin Wang,
Hong Xia Wang,
You Hua Xie,
Gang Pei,
Jia Rui Wu,
Bing Sun
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ABSTRACT: The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is an important viral structural protein. Based on bioinformatics analysis, 10 antigenic peptides derived from the S protein sequence were selected and synthesized. The antigenicity and immunoreactivity of all the peptides were tested in vivo and in vitro. Four peptides (P6, P8, P9 and P10) which contain B cell epitopes of the S protein were identified, and P8 peptide was confirmed in vivo to have a potential in serological diagnosis. By using a syncytia formation model, we tested the neutralization ability of all 10 peptides and their corresponding antibodies. It is interesting to find that P8 and P9 peptides inhibited syncytia formation, suggesting that the P8 and P9 spanning regions may provide a good target for anti-SARS-CoV drug design. Our data suggest that we have identified peptides derived from the S protein of SARS-CoV, which are useful for SARS treatment and diagnosis.
FEBS Letters 05/2005; 579(10):2130-6. · 3.54 Impact Factor
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ABSTRACT: Psoriasis is a chronic skin disease triggered by genetic, environment or other risk factors such as infection, drugs, stress, moisture, alcohol, and smoking. A major psoriasis susceptibility locus at 6p21.3 has been identified. Further studies found that HLA-DQA1*0201 allele was associated with psoriasis. However, there were few data exploring an association between the environmental factors and susceptibility genes. In this study, the samples of 189 patients with psoriasis and 333 healthy controls were collected with their consent and were carried on analysis through polymerase chain reaction sequence-specific primer (PCR-SSP) method. The proportion of male psoriasis patients engaging in the smoking and alcohol was much higher than that of the control group (P<0.005). The HLA-DQA1*0201 allele was present at significantly higher frequency in the patients with psoriasis (OR=4.25, P<1.0 x 10(-6)). Association was found between smoking, alcohol and HLA-DQA1*0201 in male patients with psoriasis (OR>6.91, P<1.0 x 10(-4)).
Acta Biochimica et Biophysica Sinica 09/2004; 36(9):597-602. · 1.38 Impact Factor
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Ying-Jia Shen,
Hua Jiang,
Jian-Peng Jin,
Zai-Bao Zhang,
Biao Xi,
You-Yu He,
Guan Wang,
Chen Wang,
Lily Qian,
Xiang Li,
Qing-Bo Yu,
Hui-Juan Liu,
De-Hui Chen,
Jian-Hua Gao,
Hai Huang, Tie-Liu Shi,
Zhong-Nan Yang
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ABSTRACT: DNA polymorphism is the basis to develop molecular markers that are widely used in genetic mapping today. A genome-wide rice (Oryza sativa) DNA polymorphism database has been constructed in this work using the genomes of Nipponbare, a cultivar of japonica, and 93-11, a cultivar of indica. This database contains 1,703,176 single nucleotide polymorphisms (SNPs) and 479,406 Insertion/Deletions (InDels), approximately one SNP every 268 bp and one InDel every 953 bp in rice genome. Both SNPs and InDels in the database were experimentally validated. Of 109 randomly selected SNPs, 107 SNPs (98.2%) are accurate. PCR analysis indicated that 90% (97 of 108) of InDels in the database could be used as molecular markers, and 68% to 89% of the 97 InDel markers have polymorphisms between other indica cultivars (Guang-lu-ai 4 and Long-te-pu B) and japonica cultivars (Zhong-hua 11 and 9522). This suggests that this database can be used not only for Nipponbare and 93-11, but also for other japonica and indica cultivars. While validating InDel polymorphisms in the database, a set of InDel markers with each chromosome 3 to 5 marker was developed. These markers are inexpensive and easy to use, and can be used for any combination of japonica and indica cultivars used in this work. This rice DNA polymorphism database will be a valuable resource and important tool for map-based cloning of rice gene, as well as in other various research on rice (http://shenghuan.shnu.edu.cn/ricemarker).
Plant physiology 08/2004; 135(3):1198-205. · 6.53 Impact Factor
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ABSTRACT: To study the immune response of host to Helicobacter pylori VacA.
The monocyte/macrophage-like U937 cells were infected with Helicobacter pylori vacA-positive strain NCTC 11638 or isogenic vacA-negative mutant. Differentially expressed genes were identified at 2, 6, 10, and 24 h post-infection by cDNA microarray. Differential expressions of some genes were confirmed by Northern blot.
More than 100 genes altered their mRNA expression at different time points respectively, many of which were identified to be related to immune evasion.
VacA is a crucial element for H pylori to escape from host immune defense by means of differentially regulating the expression of some related genes. These genes, previously known or unknown to be involved in the mechanism of immune evasion, deserve further investigation to unearth much more information complicated in the immune response.
World Journal of Gastroenterology 06/2004; 10(10):1528-32. · 2.47 Impact Factor
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Ying Lin,
Xu Shen,
Rui Fu Yang,
Yi Xue Li,
Yong Yong Ji,
You Yu He,
Mu De Shi,
Wei Lu, Tie Liu Shi,
Jin Wang,
Hong Xia Wang,
Hua Liang Jiang,
Jian Hua Shen,
You Hua Xie,
Yuan Wang,
Gang Pei,
Bei Fen Shen,
Jia Rui Wu,
Bing Sun
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ABSTRACT: The nucleocapsid (N) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) is a major virion structural protein. In this study, two epitopes (N1 and N2) of the N protein of SARS-CoV were predicted by bioinformatics analysis. After immunization with two peptides, the peptides-specific antibodies were isolated from the immunized rabbits. The further experiments demonstrated that N1 peptide-induced polyclonal antibodies had a high affinity to bind to E. coli expressed N protein of SARS-CoV. Furthermore, it was confirmed that N1 peptide-specific IgG antibodies were detectable in the sera of severe acute respiratory syndrome (SARS) patients. The results indicated that an epitope of the N protein has been identified and N protein specific Abs were produced by peptide immunization, which will be usefull for the study of SARS-CoV.
Cell Research 07/2003; 13(3):141-5. · 8.19 Impact Factor
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Lei Qin,
Bin Xiong,
Cheng Luo,
Zong-Ming Guo,
Pei Hao,
Jiong Su,
Peng Nan,
Ying Feng,
Yi-Xiang Shi,
Xiao-Jing Yu, [......],
Kai-Xian Chen,
Xu Shen,
Jian-Hua Shen,
Jian-Ping Zou,
Guo-Ping Zhao, Tie-Liu Shi,
Wei-Zhong He,
Yang Zhong,
Hua-Liang Jiang,
Yi-Xue Li
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ABSTRACT: To predict the probable genomic packaging signal of SARS-CoV by bioinformatics analysis. The derived packaging signal may be used to design antisense RNA and RNA interfere (RNAi) drugs treating SARS.
Based on the studies about the genomic packaging signals of MHV and BCoV, especially the information about primary and secondary structures, the putative genomic packaging signal of SARS-CoV were analyzed by using bioinformatic tools. Multi-alignment for the genomic sequences was performed among SARS-CoV, MHV, BCoV, PEDV and HCoV 229E. Secondary structures of RNA sequences were also predicted for the identification of the possible genomic packaging signals. Meanwhile, the N and M proteins of all five viruses were analyzed to study the evolutionary relationship with genomic packaging signals.
The putative genomic packaging signal of SARS-CoV locates at the 3' end of ORF1b near that of MHV and BCoV, where is the most variable region of this gene. The RNA secondary structure of SARS-CoV genomic packaging signal is very similar to that of MHV and BCoV. The same result was also obtained in studying the genomic packaging signals of PEDV and HCoV 229E. Further more, the genomic sequence multi-alignment indicated that the locations of packaging signals of SARS-CoV, PEDV, and HCoV overlaped each other. It seems that the mutation rate of packaging signal sequences is much higher than the N protein, while only subtle variations for the M protein.
The probable genomic packaging signal of SARS-CoV is analogous to that of MHV and BCoV, with the corresponding secondary RNA structure locating at the similar region of ORF1b. The positions where genomic packaging signals exist have suffered rounds of mutations, which may influence the primary structures of the N and M proteins consequently.
Acta Pharmacologica Sinica 07/2003; 24(6):489-96. · 1.95 Impact Factor
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Xiao-Jing Yu,
Cheng Luo,
Jian-Cheng Lin,
Pei Hao,
You-Yu He,
Zong-Ming Guo,
Lei Qin,
Jiong Su,
Bo-Shu Liu,
Yin Huang, [......],
Gang Pei,
Kai-Xian Chen,
Xu Shen,
Jian-Hua Shen,
Jian-Ping Zou,
Wei-Zhong He, Tie-Liu Shi,
Yang Zhong,
Hua-Liang Jiang,
Yi-Xue Li
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ABSTRACT: To obtain the information of ligand-receptor binding between the S protein of SARS-CoV and CD13, identify the possible interacting domains or motifs related to binding sites, and provide clues for studying the functions of SARS proteins and designing anti-SARS drugs and vaccines.
On the basis of comparative genomics, the homology search, phylogenetic analyses, and multi-sequence alignment were used to predict CD13 related interacting domains and binding sites in the S protein of SARS-CoV. Molecular modeling and docking simulation methods were employed to address the interaction feature between CD13 and S protein of SARS-CoV in validating the bioinformatics predictions.
Possible binding sites in the SARS-CoV S protein to CD13 have been mapped out by using bioinformatics analysis tools. The binding for one protein-protein interaction pair (D757-R761 motif of the SARS-CoV S protein to P585-A653 domain of CD13) has been simulated by molecular modeling and docking simulation methods.
CD13 may be a possible receptor of the SARS-CoV S protein, which may be associated with the SARS infection. This study also provides a possible strategy for mapping the possible binding receptors of the proteins in a genome.
Acta Pharmacologica Sinica 07/2003; 24(6):481-8. · 1.95 Impact Factor
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Bin Xiong,
Chun-Shan Gui,
Xiao-Ying Xu,
Cheng Luo,
Jing Chen,
Hai-Bin Luo,
Li-Li Chen,
Guo-Wei Li,
Tao Sun,
Chang-Ying Yu, [......],
Wen-Hu Duan,
Jing-Kang Shen,
Lei Qin, Tie-Liu Shi,
Yi-Xue Li,
Kai-Xian Chen,
Xiao-Min Luo,
Xu Shen,
Jian-Hua Shen,
Hua-Liang Jiang
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ABSTRACT: To constructed a three-dimensional (3D) model for the 3C like (3CL) proteinase of SARS coronavirus (SARS-CoV), and to design inhibitors of the 3CL proteinase based on the 3D model.
Bioinformatics analyses were performed to search the homologous proteins of the SARS-CoV 3CL proteinase from the GenBank and PDB database. A 3D model of the proteinase was constructed by using homology modeling technique. Targeting to the 3D model and its X-ray crystal structure of the main proteinase (Mpro) of transmissible gastroenteritis virus (TGEV), virtual screening was performed employing molecular docking method to identify possible 3CL proteinase inhibitors from small molecular databases.
Sequence alignment indicated that the SARS-CoV 3CL proteinase was extremely homologous to TGEV Mpro, especially the substrate-binding pocket (active site). Accordingly, a 3D model for the SARS-CoV 3CL proteinase was constructed based on the crystal structure of TGEV Mpro. The 3D model adopts a similar fold of the TGEV Mpro, its structure and binding pocket feature are almost as same as that of TGEV Mpro. The tested virtual screening indicated that 73 available proteinase inhibitors in the MDDR database might dock into both the binding pockets of the TGEV Mpro and the SARS-CoV 3CL proteinase.
Either the 3D model of the SARS-CoV 3CL proteinase or the X-ray crystal structure of the TGEV Mpro may be used as a starting point for design anti-SARS drugs. Screening the known proteinase inhibitors may be an appreciated shortcut to discover anti-SARS drugs.
Acta Pharmacologica Sinica 07/2003; 24(6):497-504. · 1.95 Impact Factor
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Xu Shen,
Jian-Hua Xue,
Chang-Ying Yu,
Hai-Bin Luo,
Lei Qin,
Xiao-Jing Yu,
Jing Chen,
Li-Li Chen,
Bin Xiong,
Li-Duo Yue,
Jian-Hua Cai,
Jian-Hua Shen,
Xiao-Min Luo,
Kai-Xian Chen, Tie-Liu Shi,
Yi-Xue Li,
Geng-Xi Hu,
Hua-Liang Jiang
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ABSTRACT: To obtain the pure sample of SARS small envelope E protein (SARS E protein), study its properties and analyze its possible functions.
The plasmid of SARS E protein was constructed by the polymerase chain reaction (PCR), and the protein was expressed in the E coli strain. The secondary structure feature of the protein was determined by circular dichroism (CD) technique. The possible functions of this protein were annotated by bioinformatics methods, and its possible three-dimensional model was constructed by molecular modeling.
The pure sample of SARS E protein was obtained. The secondary structure feature derived from CD determination is similar to that from the secondary structure prediction. Bioinformatics analysis indicated that the key residues of SARS E protein were much conserved compared to the E proteins of other coronaviruses. In particular, the primary amino acid sequence of SARS E protein is much more similar to that of murine hepatitis virus (MHV) and other mammal coronaviruses. The transmembrane (TM) segment of the SARS E protein is relatively more conserved in the whole protein than other regions.
The success of expressing the SARS E protein is a good starting point for investigating the structure and functions of this protein and SARS coronavirus itself as well. The SARS E protein may fold in water solution in a similar way as it in membrane-water mixed environment. It is possible that beta-sheet I of the SARS E protein interacts with the membrane surface via hydrogen bonding, this beta-sheet may uncoil to a random structure in water solution.
Acta Pharmacologica Sinica 07/2003; 24(6):505-11. · 1.95 Impact Factor
