inhibition of the drug metabolizing enzymes—the undesirable inhibition
Báo cáo y học: "Polymorphisms of two histamine-metabolizing enzymes genes and childhood allergic asthma: a case control study" doc
... variation of histamine metabolism might contribute to the pathophysiology of asthma The aim of our study was to analyze a relationship between the polymorphisms of two genes encoding histamine metabolizing ... Although they were found to slightly alter enzyme kinetics by increasing the Km of the ABP1 enzyme, no significant changes were observed in relation to the genotypes of those two SNPs [9] The importance ... in the group of asthmatic children in comparison to the control group (Table 1) When we analyzed our group according to gender, we also observed the association of TT genotype in the group of...
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Tài liệu Báo cáo khoa học: Substrate specificity and inhibition of brassinin hydrolases, detoxifying enzymes from the plant pathogens Leptosphaeria maculans and Alternaria brassicicola ppt
... both BHs The type of inhibition caused by cyclobrassinin was determined from the kinetics of inhibition of BHs, shown in the form of Lineweaver–Burk double reciprocal plots (Fig 8B,C) These results ... BHAb The temperature dependence of the activities of the BHs was tested in the range 5–56 °C; the apparent optimum temperatures of BHLmL2 were 25–30 °C FEBS Journal 276 (2009) 7412–7428 ª 2009 The ... and 85% inhibition of BHLmL2 and BHAb, respectively, while mm 2-mer- captoethanol caused 85% and 97% inhibition of BHLmL2 and BHAb, respectively The influence of pH on the activities of the BH...
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Tài liệu Báo cáo khoa học: Treatment of neutral glycosphingolipid lysosomal storage diseases via inhibition of the ABC drug transporter, MDR1 Cyclosporin A can lower serum and liver globotriaosyl ceramide levels in the Fabry mouse model doc
... disease, the primary pathology is in the kidney [1], the major site of Gb3 synthesis in man [11], and in the heart, possibly due to the association of Gb3 synthesis with the microvasculature GSL synthesis ... synthesis in the Fabry mouse model Our studies have further delineated the abnormal Gb3 synthesis in this model and have shown that the inhibition of MDR1 is a viable potential approach to the ... considered that the increased renal Gb3 of the Fabry mouse might extend to the glomerulus to provide a model of the human disease In the cortex of wild-type kidney, subpopulations of renal tubules...
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Tài liệu Báo cáo khoa học: Mechanism of dihydroneopterin aldolase NMR, equilibrium and transient kinetic studies of the Staphylococcus aureus and Escherichia coli enzymes docx
... set of control data was obtained in the absence of the protein The data set obtained in the absence of the protein was then subtracted from the corresponding data set obtained in the presence of ... performed in the absence of the ligand The control data set obtained in the absence of the ligand was subtracted from the corresponding data set obtained in the presence of the ligand The Kd values ... cleavage of the bond between 1¢ and 2¢ carbons of the substrate The epimerization product is generated by the re-formation of the C–C bond after the reorientation of GA, which exposes the opposite...
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Tài liệu Báo cáo khoa học: Evolutionary relationships of the prolyl oligopeptidase family enzymes docx
... With respect to the studied enzymes of the POP family, POP seems to be the most conserved enzyme Ten conserved amino acids were found at the active site of the enzyme of each of the studied POP ... ACPH and DPP IV The whole bar and the lower part of the bar represent the similarity percentages of the catalytic domains and the complete sequences, respectively present in the last universal ... our analysis of subsite evolution, the specificity might be achieved by varying the structures of P2 and P3, but not the P1 subsite of the inhibitor The most interesting amino acid at the S3 subsite...
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Tài liệu Báo cáo Y học: Inhibition of the MEK/ERK signaling pathway by the novel antimetastatic agent NAMI-A down regulates c-myc gene expression and endothelial cell proliferation ppt
... bromide stained gels of the reaction products obtained using lL of the RT products after 30 cycles of PCR amplification The lower part of panel A, and panels B, C report the expression of c-myc mRNA ... cells, indicating the capability of both drugs to selectively inhibit the PMA-dependent signaling leading to the phosphorylation of ERK1/2 isoenzymes (Fig 2B) To verify the involvement of a PKC-dependent ... expression To establish whether the decrease in c-myc mRNA expression elicited by NAMI-A might have occurred at the transcriptional level, we assessed the rate of transcription of the c-myc gene by using...
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Tài liệu Báo cáo khoa học: The molecular surface of proteolytic enzymes has an important role in stability of the enzymatic activity in extraordinary environments pptx
... wild-type ALP I On the other hand, the Tm of D266N/Y269A-ALP I increased by only °C The denaturation temperature indicates the stability of the structure of the protein The difference of the increments ... surrounding residues of the depression, and the side chain of the mutated residue might restrain the mobility of the N-terminal region on the surface by interaction with the main chain of Lys26 by van ... wildtype enzyme, the side chain of Asp266 interacted with the amino group of the main chain at Glu268 The oxygen of the main chain at Asp266 was bound to amino groups of main chain of Tyr269 and...
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Tài liệu Báo cáo Y học: Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants pdf
... [106], these cases are relatively easy to explain as above But if one considers the evolution of all of the enzymes of the pathway (Fig 4), it is clear that only about half of the enzymes of the ... obtain an overview of the patterns of similarity for the enzymes of these pathways in plants and the relationships of their differentially compartmentalized isoenzymes Condensing the information ... to the cytosol of the host [3,83] For the tricarboxylic acid cycle, a complete transfer of the pathway to the cytosol would not work, because some of its enzymes are intergral components of the...
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Báo cáo khoa học: Substrate preference and phosphatidylinositol monophosphate inhibition of the catalytic domain of the Per-Arnt-Sim domain kinase PASKIN ppt
... phosphorylation of a microarray of 1176 peptides in the presence of [c-33P]ATP The magnified inset shows an example of the results obtained after detection by phosphorimaging (B) Peptide sequences of the ... translocation of UDPglucose pyrophosphorylase to the plasma membrane, where it increases cell wall glucan synthesis at the expense of glycogen storage In the absence of PSKs, glycogen rather than ... MEFs (data not shown) On the basis of the known functions of the PASKIN-related FixL oxygen sensor in bacteria and the PASKIN orthologues in yeast, and considering the lack of any obvious phenotype...
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Báo cáo khoa học: Analysis of the NADH-dependent retinaldehyde reductase activity of amphioxus retinol dehydrogenase enzymes enhances our understanding of the evolution of the retinol dehydrogenase family pot
... respectively [29] The overall analysis, examining the topology of the phylogenetic tree and the position of each gene inside the cluster, was informative regarding the orthology relationships of the distinct ... vertebrate enzymes The most significant difference between the amphioxus and the other retinal reductases was, nevertheless, their preference for the NADH cofactor To our knowledge, these are the first SDR ... on the cytosolic side of the membrane [38,39] Amphioxus RDH did not show positively charged amino acids at the N-terminus of the signaling sequence, but rather contained the L24ERGR motif at the...
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Báo cáo khoa học: The Saccharomyces cerevisiae orthologue of the human protein phosphatase 4 core regulatory subunit R2 confers resistance to the anticancer drug cisplatin pot
... subunit of Pph3p required for the binding of Psy2p, we examined the sensitivity of the YBL046w ⁄ Psy4p deletion strain to cisplatin The comparable increased sensitivities to cisplatin of the homozygous ... identical to those of the wild-type cells Examination of the phenotype of S cerevisiae carrying deletions for both the YBL046w gene and the TUB2 gene Since decreased expression of Ppp4c in D melanogaster ... outside this region, the proteins are difficult to align because identity between the two proteins is low Nevertheless, the alignment in Fig shows that the overall similarity of the protein encoded...
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Báo cáo khoa học: MR solution structure of the precursor for carnobacteriocin B2, an antimicrobial peptide fromCarnobacterium piscicola Implications of the a-helical leader section for export and inhibition of type IIa bacteriocin activity pdf
... help determine the structural basis of the inhibition of the antimicrobial activity of CbnB2 by the leader and to assist future analysis of the interaction of preCbnB2 with its ABC transporter ... for cleavage of the leader peptide after the double glycine motif [16,17] This cleavage occurs on the cytoplasmic side of the membrane during export of the bioactive peptide [18] The leader peptide ... establish the preferred geometry of the precursor We now report the chemical synthesis, biochemical production, and solution structure of preCbnB2, and compare it with the structure of the mature...
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Báo cáo khoa học: Kinetics of the inhibition of neutrophil proteinases by recombinant elafin and pre-elafin (trappin-2) expressed in Pichia pastoris ppt
... further characterized To limit the appearance of the 13 kDa clipped form of trappin-2 for the large-scale production of trappin-2, the duration of fermentation was reduced to three days Under these ... 0.02 s)1 for the inhibition of PR3 by 1.6 lM rectrappin-2 Accurate values of kdiss could not be calculated using Eqn (4) because of the almost complete inhibition of HNE and PR3 once the steady ... regression analysis of the data using Eqn (7) and using the best estimate of kdiss governing the dissociation of the HNErecelan complex Good ts were also obtained for the three other enzymeinhibitor...
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Báo cáo Y học: Modulation of the oligomeric structures of HIV-1 retroviral enzymes by synthetic peptides and small molecules pptx
... vitro In these authors’ opinions, such studies obviously represent the next logical step in the unfolding story of the modulation of the oligomeric structures of HIV-1 viral enzymes by synthetic ... aminoacid residues at the N- and C-termini of PR contribute close to 75% of the total Gibbs energy [15] The importance of this four-stranded b sheet is further emphasized by the fact that all PR ... plasmid (that contains the selection module kPR-lacZ-tet and directs the production of the cI-PR fusion protein), cI-PR represses the transcription of the reporter genes and the transformants show...
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Báo cáo Y học: Baboon cytochrome P450 17a-hydroxylase/17,20-lyase (CYP17) Characterization of the adrenal microsomal and cloned enzymes docx
... [3,4] The dual activity of CYP17 and the differential regulation thereof have been the subject of many studies It is apparent that the normal expression and dual hydroxylase and lyase activities of ... Before the addition and (B) after the addition of NADH to the reference cuvette The reduction in the peak at 425 nm after addition of NADH is indicative of the presence of cytochrome b5 (C) NADH reduced ... respect to the interaction of the enzyme with the 17-hydroxylated intermediate Baboon CYP17 initially converted most of the PREG to 17-OHPREG and during the entire experiment, the ratio of DHEA/17-OHPREG...
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Báo cáo khoa học: Inhibition of the NF-jB transcriptional activity by protein kinase A pot
... abolish the inhibitory effect of PKA on NF-jB (Fig 5B) In this study, we have demonstrated the evidence that the C-terminal transactivation domain of p65 is responsible for the inhibition of NF-jB ... conflicting evidences regarding the action of PKA on the NF-jB activity Although the majority of reports [10–14] including this study, demonstrated the inhibitory actions of PKA on the NF-jB dependent gene ... inhibit TNFa-induced DNA-binding of NF-jB (Fig 3D) Thus, it is likely that the inhibitory effect of PKA on NF-jB is not due to the inhibition of DNA-binding activity of NF-jB PKA activation does...
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Báo cáo Y học: Inhibition of the SERCA Ca21 pumps by curcumin Curcumin putatively stabilizes the interaction between the nucleotide-binding and phosphorylation domains in the absence of ATP pot
... 3B) in the absence and presence of curcumin, using the coupled enzyme assay In Fig 3A, the half-maximal activation of the ATPase by Ca2þ was measured in the absence of and in the presence of 10 ... [32P]ATP in the absence of Ca2þ (Fig 4A) The data showed that the amount of ATP bound to the ATPase was reduced by curcumin The binding inhibition had a apparent Ki (IC50) of about mM Reversing the ... side of the membrane While in the E2 form the Ca2þ binding sites have translocated across the membrane to the luminal side and are of low affinity Furthermore, in the E1 conformational state, the...
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Báo cáo Y học: Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor analogues pdf
... stabilize the binding of inhibitors to TM-3 are as follows (a) The Trp indole ring of the inhibitors is stacked against the imidazole ring of His143 in the S)1 pocket of the proteinase (b) The middle ... from the comparisons of the synthetic inhibitor analogues show that the P)1 Trp residue of the inhibitors is primarily specific for binding to TM-3 The side chain of the middle residue in the inhibitor ... 2002 Inhibition of a SVMP by its endogenous inhibitors (Eur J Biochem 269) 3051 Fig Stereoview of the interaction of TM-3 with pENW (A) The binding of the inhibitor to TM-3 (B) The unbound TM-3 The...
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Báo cáo khoa học: ATP-binding domain of heat shock protein 70 is essential for its effects on the inhibition of the release of the second mitochondria-derived activator of caspase and apoptosis in C2C12 cells potx
... respect to the role of HSP70 in the inhibition of the release of Smac and apoptosis GAPDH Ratio of HSP70 to GAPDH 14 # 12 # 10 * The role of the ATP-binding domain of HSP70 in the prevention of the ... including the inhibition of the activation of caspases-9 and -3 (Fig 6A) after exposure to H2O2 for h, as well as the inhibition of H2O2induced apoptosis as assessed by the percentage of apoptotic ... domain of HSP70 is essential for the inhibition of H2O2-induced activation of caspases-9 and -3 and apoptosis (A) The effects of HSP70 and its deletion mutant proteins on the activation of caspases-9...
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Báo cáo khoa học: A characteristic Glu17 residue of pig carnitine palmitoyltransferase 1 is responsible for the low Km for carnitine and the low sensitivity to malonyl-CoA inhibition of the enzyme docx
... and expression of the liver and muscle isoforms of ovine carnitine palmitoyltransferase 1: residues within the N-terminus of the muscle isoform influence the kinetic properties of the enzyme Biochem ... with the human or pig C-terminal region of the enzymes Sequence alignment of the first 50 N-terminal amino acids of CPT1 shows the high degree of identity between these enzymes (Fig 3A) In fact, the ... ascertain whether the presence of a negative domain in the N-terminal region of the pig enzyme could be responsible for its low level of malonyl-CoA inhibition, we determined the IC50 of wild-type...
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