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111.
India's biotechnology industry has been growing towards new heights in conjunction with the recent economic outburst. The country has the potential to revolutionize biopharmaceutical and healthcare sectors. In this review, we have highlighted the achievements of India's biotechnology industry, especially biopharmaceutical and healthcare sectors that include therapeutics, diagnostics, stem cell research, human healthcare related bioinformatics and animal health care. We have also described regulatory mechanisms involved in India's health care biotech including manpower development. 相似文献
112.
Clemente JC Coman RM Thiaville MM Janka LK Jeung JA Nukoolkarn S Govindasamy L Agbandje-McKenna M McKenna R Leelamanit W Goodenow MM Dunn BM 《Biochemistry》2006,45(17):5468-5477
A series of HIV-1 protease mutants has been designed in an effort to analyze the contribution to drug resistance provided by natural polymorphisms as well as therapy-selective (active and non-active site) mutations in the HIV-1 CRF_01 A/E (AE) protease when compared to that of the subtype B (B) protease. Kinetic analysis of these variants using chromogenic substrates showed differences in substrate specificity between pretherapy B and AE proteases. Inhibition analysis with ritonavir, indinavir, nelfinavir, amprenavir, saquinavir, lopinavir, and atazanavir revealed that the natural polymorphisms found in A/E can influence inhibitor resistance. It was also apparent that a high level of resistance in the A/E protease, as with B protease, is due to it aquiring a combination of active site and non-active site mutations. Structural analysis of atazanavir bound to a pretherapy B protease showed that the ability of atazanavir to maintain its binding affinity for variants containing some resistance mutations is due to its unique interactions with flap residues. This structure also explains why the I50L and I84V mutations are important in decreasing the binding affinity of atazanavir. 相似文献
113.
Heat shock-induced attenuation of hydroxyl radical generation and mitochondrial aconitase activity in cardiac H9c2 cells 总被引:2,自引:0,他引:2
Ilangovan G Venkatakrishnan CD Bratasz A Osinbowale S Cardounel AJ Zweier JL Kuppusamy P 《American journal of physiology. Cell physiology》2006,290(2):C313-C324
A mild heat shock (hyperthermia) protects cells from apoptotic and necrotic deaths by inducing overexpression of various heat shock proteins (Hsps). These proteins, in combination with the activation of the nitric oxide synthase (NOS) enzyme, play important roles in the protection of the myocardium against a variety of diseases. In the present work we report that the generation of potent reactive oxygen species (ROS), namely ·OH in cardiac H9c2 cells, is attenuated by heat shock treatment (2 h at 42°C). Western blot analyses showed that heat shock treatment induced overexpression of Hsp70, Hsp60, and Hsp25. The observed ·OH was found to be derived from the superoxide (O2·) generated by the mitochondria. Whereas the manganese superoxide dismutase (MnSOD) activity was increased in the heat-shocked cells, the mitochondrial aconitase activity was reduced. The mechanism of O2· conversion into ·OH in mitochondria is proposed as follows. The O2· leaked from the electron transport chain, oxidatively damages the mitochondrial aconitase, releasing a free Fe2+. The aconitase-released Fe2+ combines with H2O2 to generate ·OH via a Fenton reaction and the oxidized Fe3+ recombines with the inactivated enzyme after being reduced to Fe2+ by other cellular reductants, turning it over to be active. However, in heat-shocked cells, because of higher MnSOD activity, the excess H2O2 causes irreversible damage to the mitochondrial aconitase enzyme, thus inhibiting its activity. In conclusion, we propose that attenuation of ·OH generation after heat shock treatment might play an important role in reducing the myocardial ischemic injury, observed in heat shock-treated animals. proteins; free radicals; spin trapping; reactive oxygen species 相似文献
114.
Adeno-associated virus type 2 contains an integrin alpha5beta1 binding domain essential for viral cell entry
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Asokan A Hamra JB Govindasamy L Agbandje-McKenna M Samulski RJ 《Journal of virology》2006,80(18):8961-8969
Integrins have been implicated as coreceptors in the infectious pathways of several nonenveloped viruses. For example, adenoviruses are known to interact with alphaV integrins by virtue of a high-affinity arginine-glycine-aspartate (RGD) domain present in the penton bases of the capsids. In the case of adeno-associated virus type 2 (AAV2), which lacks this RGD motif, integrin alphaVbeta5 has been identified as a coreceptor for cellular entry. However, the molecular determinants of AAV2 capsid-integrin interactions and the potential exploitation of alternative integrins as coreceptors by AAV2 have not been established thus far. In this report, we demonstrate that integrin alpha5beta1 serves as an alternative coreceptor for AAV2 infection in human embryonic kidney 293 cells. Such interactions appear to be mediated by a highly conserved domain that contains an asparagine-glycine-arginine (NGR) motif known to bind alpha5beta1 integrin with moderate affinity. The mutation of this domain reduces transduction efficiency by an order of magnitude relative to that of wild-type AAV2 vectors in vitro and in vivo. Further characterization of mutant and wild-type AAV2 capsids through transduction assays in cell lines lacking specific integrins, cell adhesion studies, and cell surface/solid-phase binding assays confirmed the role of the NGR domain in promoting AAV2-integrin interactions. Molecular modeling studies suggest that NGR residues form a surface loop close to the threefold axis of symmetry adjacent to residues previously implicated in binding heparan sulfate, the primary receptor for AAV2. The aforementioned results suggest that the internalization of AAV2 in 293 cells might follow a "click-to-fit" mechanism that involves the cooperative binding of heparan sulfate and alpha5beta1 integrin by the AAV2 capsids. 相似文献
115.
Molecular characterization of the heparin-dependent transduction domain on the capsid of a novel adeno-associated virus isolate, AAV(VR-942)
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Schmidt M Govindasamy L Afione S Kaludov N Agbandje-McKenna M Chiorini JA 《Journal of virology》2008,82(17):8911-8916
A new adeno-associated virus (AAV), referred to as AAV(VR-942), has been isolated as a contaminant of adenovirus strain simian virus 17. The sequence of the rep gene places it in the AAV serotype 2 (AAV2) complementation group, while the capsid is only 88% identical to that of AAV2. High-level AAV(VR-942) transduction activity requires cell surface heparan sulfate proteoglycans, although AAV(VR-942) lacks residues equivalent to the AAV2 R585 and R588 amino acid residues essential for mediating the interaction of AAV2 with the heparan sulfate proteoglycan receptor. Instead, AAV(VR-942) uses a distinct transduction region. This finding shows that distinct domains on different AAV isolates can be responsible for the same activities. 相似文献
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Chiranjib Chakraborty Minna J. Hsu Govindasamy Agoramoorthy 《Cell biochemistry and biophysics》2014,70(2):907-922
The occurrence of type 2 diabetes (T2D) accounts for 90–95 % of all diabetes. Intestine hormone glucagon-like peptide-1 (GLP-1) has an antidiabetic role that enhances insulin secretion and pancreatic β-cell proliferation. GLP-1 is degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) rapidly. Hence, the DPP-4 inhibition has been preferred not only for the treatment but also as a major drug target. Sitagliptin and Diprotin-A are antihyperglycemic agents for the treatment of T2D. However, little is known on the molecular dynamics of DPP-4 and the interaction properties with its ligands, namely Sitagliptin and Diprotin-A. This study has used the latest bioinformatic tools to understand the molecular dynamics and its interaction properties of DPP-4. This study has explored the number of α helices, β strands, β hairpins, Ψ loop, β bulges, β turns, and ? turns and they were 19, 46, 25, 1, 14, 70, and 4, respectively. The highest number of H-bonds was recorded in α helix of domain-1, and the lowest number H-bonds were noted in α helix of domain-2. During interaction between residues, in A- and B-chain, 47 and 48 residues are involved for interaction, and interaction interface area was more in A-Chain (2176 Å2). From DPP-4 and Sitagliptin interaction, three residues in active sites such as Try226, Glu205, and Glu206 were involved in three H-bond formation, while 10 other amino acids (Try547, Try667, Asn710, Val711, His740, Ser630, Ser209, Arg358, Phe357, and Val207) were involved in hydrophobic interactions. In this review, we have shown the importance of bioinformatics as an excellent tool for a rapid method to assess the molecular dynamics and its interaction properties of DPP-4. Our predictions highlighted in this review will help researchers to understand the interaction properties and recognition of interactive sites to design more DPP-4 inhibitors for the treatment of T2D and drug discovery. 相似文献
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