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61.
Rubinder K Chadha BS Singh N Saini HS Singh S 《Journal of industrial microbiology & biotechnology》2002,29(2):70-74
Thermomyces lanuginosus was subjected to three cycles of mutagenesis (UV/NTG) and a selection procedure to develop amylase-hyperproducing, catabolite-repression-resistant
and partially constitutive strains. One of the selected derepressed mutant strain III51, produced ∼7- and 3-fold higher specific activity of α-amylase (190 U/mg protein) and glucoamylase (105 U/mg protein), respectively,
compared to a wild-type parental strain. Further, the effect of production parameters on mutant strain III51 was studied using a Box–Behnken design. The regression models computed showed significantly high R
2 values of 96 and 97% for α-amylase and glucoamylase activities, respectively, indicating that they are appropriate for predicting
relationships between corn flour, soybean meal and pH with α-amylase and glucoamylase production. Journal of Industrial Microbiology & Biotechnology (2002) 29, 70–74 doi:10.1038/sj.jim.7000270
Received 05 July 2001/ Accepted in revised form 16 April 2002 相似文献
62.
Lactoferrin was purified from fresh samples of goat colostrums, saturated with Fe3+ and CO3(2-) ions and crystallized by microdialysis method. The crystals belong to orthorhombic space group P2(1)2(1)2(1) with a=104.6 A, b=153.8 A, c=155.1 A and Z=4. The quality of crystals was poor, thus the intensity data were restricted to 4.0 A resolution only. The structure was determined by molecular replacement method using diferric buffalo lactoferrin as a model. The solution clearly indicated the presence of one molecule in the asymmetric unit, which corresponds to a Vm value of 7.1 A3/Da. The structure was refined with stringent constraints to an R-factor of 0.246 using all the reflections 15,870 to 4.0 A resolution. The overall structure of goat lactoferrin is essentially similar to those of buffalo and bovine lactoferrins. However, the iron-binding environment in goat lactoferrin is somewhat different, in which 2 CO3(2-). ions have low occupancies. The solvent content of approximately 84% was very high in the present case which explains the fragility of the crystals of goat lactoferrin. In a way, it is very surprising that the crystals grow at all, although crystals with solvent as high as 89% have been reported. 相似文献
63.
Khanna S Venojarvi M Roy S Sharma N Trikha P Bagchi D Bagchi M Sen CK 《Free radical biology & medicine》2002,33(8):1089-1096
64.
Dhanvantari S Shen FS Adams T Snell CR Zhang C Mackin RB Morris SJ Loh YP 《Molecular endocrinology (Baltimore, Md.)》2003,17(9):1856-1867
In familial hyperproinsulinemia, specific mutations in the proinsulin gene are linked with a profound increase in circulating plasma proinsulin levels. However, the molecular and cellular basis for this disease remains uncharacterized. Here we investigated how these mutations may disrupt the sorting signal required to target proinsulin to the secretory granules of the regulated secretory pathway, resulting in the unregulated release of proinsulin. Using a combination of molecular modeling and site-directed mutagenesis, we have identified structural molecular motifs in proinsulin that are necessary for correct sorting into secretory granules of endocrine cells. We show that membrane carboxypeptidase E (CPE), previously identified as a prohormone-sorting receptor, is essential for proinsulin sorting. This was demonstrated through short interfering RNA-mediated depletion of CPE and transfection with a dominant negative mutant of CPE in a beta-cell line. Mutant proinsulins found in familial hyperproinsulinemia failed to bind to CPE and were not sorted efficiently. These findings provide evidence that the elevation of plasma proinsulin levels found in patients with familial hyperproinsulinemia is caused by the disruption of CPE-mediated sorting of mutant proinsulins to the regulated secretory pathway. 相似文献
65.
The polyphemusins present in the hemocytes of the horsechoe crab and their structurally modified analogs have been shown to exhibit activity against HIV-1. Among the many variants, T22 ([Tyr(5,12), Lys(7)]-polyphemusin II), and its shorter and more potent analog, T140 [Arg(1)-Arg-2-Nal-Cys-Tyr(5)-Arg-Lys-D-Lys-Pro-Tyr(10)-Arg-Cit-Cys-Arg(14)] (Polyphemusin II-derived peptide), affect the HIV-cell fusion process and inhibit the T-cell line-tropic (T-tropic) HIV-1 infection. Conformational studies of polyphemusin II derived peptide have been carried out by (1)H and (13)C 2D-NMR and MD simulations in water and HFA (40%). The NMR parameters of chemical shift, temperature coefficients of the NH chemical shifts, (3)JNHalpha coupling constants and the pattern of nOe's were used to deduce the structural characteristics. Solution structures were generated using dihedral and distance restraints by MD simulations. The structures are characterized by a dominant family possessing an anti-parallel beta-pleated sheet that is constrained by the disulphide bridge between Cys4 and Cys13. The two strands of the beta-sheet are joined by a Type II' beta-turn spanning the residues Lys(7)-D-Lys(8)-Pro(9)-Tyr(10). This conformation is present in both water and HFA. The only difference in the two structures is that the beta-strands are more cohesive in HFA being firmly held by H-bonds. The solution structures generated from MD simulations were refined by MARDIGRAS to R-factors of 0.44 and 0.57 in water and HFA respectively. The conformation deduced for T140 is very similar to that reported for T22 and is thought to be associated with their anti HIV activity. 相似文献
66.
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68.
The current staus of research of free and glycosylated alkaloids occuring in members of the genus Crinum is reviewed. The distribution, isolation, spectral properties, structural properties, inter conventions and biological acitivities of these alkaloids are presented. 相似文献
69.
Pravin L. Kotian Raman Krishnan Scott Rowland Yahya El-Kattan Surendra K. Saini Ramanda Upshaw Shanta Bantia Shane Arnold Y. Sudhakar Babu Pooran Chand 《Bioorganic & medicinal chemistry》2009,17(11):3934-3958
Factor VIIa (FVIIa), a serine protease enzyme, coupled with tissue factor (TF) plays an important role in a number of thrombosis-related disorders. Inhibition of TF·FVIIa occurs early in the coagulation cascade and might provide some safety advantages over other related enzymes. We report here a novel series of substituted biphenyl derivatives that are highly potent and selective TF·FVIIa inhibitors. Parallel synthesis coupled with structure-based drug design allowed us to explore the S2 pocket of the enzyme active site. A number of compounds with IC50 value of <10 nM were synthesized. The X-ray crystal structures of some of these compounds complexed with TF·FVIIa were determined and results were applied to design the next round of inhibitors. All the potent inhibitors were tested for inhibition against a panel of related enzymes and selectivity of 17,600 over thrombin, 450 over trypsin, 685 over FXa, and 76 over plasmin was achieved. Two groups, vinyl 36b and 2-furan 36ab, were identified as the optimum binding substituents on the phenyl ring in the S2 pocket. Compounds with these two substituents are the most potent compounds in this series with good selectivity over related serine proteases. These compounds will be further explored for structure–activity relationship. 相似文献
70.
Luis M. Alvarez Jaime J. Rivera Linda Stockdale Sunil Saini Richard T. Lee Linda G. Griffith 《PloS one》2015,10(6)
Transplantation of freshly-aspirated autologous bone marrow, together with a scaffold, is a promising clinical alternative to harvest and transplantation of autologous bone for treatment of large defects. However, survival proliferation, and osteogenic differentiation of the marrow-resident stem and progenitor cells with osteogenic potential can be limited in large defects by the inflammatory microenvironment. Previous studies using EGF tethered to synthetic polymer substrates have demonstrated that surface-tethered EGF can protect human bone marrow-derived osteogenic stem and progenitor cells from pro-death inflammatory cues and enhance their proliferation without detriment to subsequent osteogenic differentiation. The objective of this study was to identify a facile means of tethering EGF to clinically-relevant βTCP scaffolds and to demonstrate the bioactivity of EGF tethered to βTCP using stimulation of the proliferative response of human bone-marrow derived mesenchymal stem cells (hBMSC) as a phenotypic metric. We used a phage display library and panned against βTCP and composites of βTCP with a degradable polyester biomaterial, together with orthogonal blocking schemes, to identify a 12-amino acid consensus binding peptide sequence, LLADTTHHRPWT, with high affinity for βTCP. When a single copy of this βTCP-binding peptide sequence was fused to EGF via a flexible peptide tether domain and expressed recombinantly in E. coli together with a maltose-binding domain to aid purification, the resulting fusion protein exhibited modest affinity for βTCP. However, a fusion protein containing a linear concatamer containing 10 repeats of the binding motif the resulting fusion protein showed high affinity stable binding to βTCP, with only 25% of the protein released after 7 days at 37oC. The fusion protein was bioactive, as assessed by its abilities to activate kinase signaling pathways downstream of the EGF receptor when presented in soluble form, and to enhance the proliferation of hBMSC when presented in tethered form on commercial βTCP bone regeneration scaffolds. 相似文献