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41.
P J Lad 《Biochemical and biophysical research communications》1980,96(1):203-210
Involvement of cholesterol in the regulation of rat lung particulate guanylate cyclase was studied with filipin. The enzyme was not activated to a great extent by sodium nitroprusside alone; however, in presence of filipin nitroprusside activated the enzyme about 12–16 fold over the basal. Filipin did not affect the soluble enzyme significantly. The changes induced by filipin did not cause solubilization of proteins or enzyme. The Arrhenius plot of filipin-treated particulate enzyme did not have a “break” which was evident with untreated enzyme. The results suggest that the sequestering of cholesterol by filipin can modulate the activity of membrane-associated guanylate cyclase probably by changing the membrane fluidity. 相似文献
42.
Dr. Lad Čelakovský 《Plant Systematics and Evolution》1872,22(8):245-253
Ohne Zusammenfassung 相似文献
43.
Dr. Lad Čelakovský 《Plant Systematics and Evolution》1874,24(2):37-45
Ohne Zusammenfassung 相似文献
44.
G H Lee J S Kaptein S J Scott H Niedzin C I Kalunta P M Lad 《The Biochemical journal》1989,262(1):165-172
Neutrophils pretreated with the chemoattractant formylmethionyl-leucyl-phenylalanine become unresponsive when re-exposed to the same ligand, a process termed desensitization. We have examined whether desensitization of transduction (Ca2+ mobilization) or of other cell functions (superoxide generation, enzyme release, or aggregation) occurs synchronously. Simultaneous studies of Ca2+ mobilization and aggregation by using Fura-2-loaded cells indicate that, under conditions where the aggregation response is abolished, most of the Ca2+ mobilization is unaltered. Further studies were then carried out to ascertain whether desensitization of Ca2+ mobilization could in fact be induced. Desensitization was observed, and was dependent on the number of exposures of the cells to the ligand, the concentration of the ligand, and whether the ligand was left in the medium or was removed. The pattern of resensitization was dependent on the experimental design. Under conditions where ligand was continuously present, no recovery of the Ca2+-mobilization response was seen with subsequent challenges. In contrast, on removal of ligand, this response showed partial recovery. Whereas complete desensitization of aggregation was noted, enzyme release showed a markedly lesser degree of desensitization and required more frequent exposures to the ligand before it was observed. Little or no desensitization of superoxide generation was observed regardless of the conditions utilized. Studies using phorbol myristate acetate as the ligand showed that Ca2+ mobilization and aggregation could be simultaneously inhibited. Our results suggest that discrete mechanisms of desensitization are possible in human neutrophils, and that desensitization of one particular function (aggregation) does not imply concomitant desensitization of other functions. 相似文献
45.
Dr. Lad Čelakovslsý 《Plant Systematics and Evolution》1874,24(5):138-140
46.
47.
Dr. Lad Čelakovský 《Plant Systematics and Evolution》1879,29(11):361-368
Ohne Zusammenfassung 相似文献
48.
Dr. Lad Čelakovský 《Plant Systematics and Evolution》1872,22(4):109-111
Ohne Zusammenfassung 相似文献
49.
Luo L Parrish CA Nevins N McNulty DE Chaudhari AM Carson JD Sudakin V Shaw AN Lehr R Zhao H Sweitzer S Lad L Wood KW Sakowicz R Annan RS Huang PS Jackson JR Dhanak D Copeland RA Auger KR 《Nature chemical biology》2007,3(11):722-726
The mitotic kinesin KSP (kinesin spindle protein, or Eg5) has an essential role in centrosome separation and formation of the bipolar mitotic spindle. Its exclusive involvement in the mitotic spindle of proliferating cells presents an opportunity for developing new anticancer agents with reduced side effects relative to antimitotics that target tubulin. Ispinesib is an allosteric small-molecule KSP inhibitor in phase 2 clinical trials. Mutations that attenuate ispinesib binding to KSP have been identified, which highlights the need for inhibitors that target different binding sites. We describe a new class of selective KSP inhibitors that are active against ispinesib-resistant forms of KSP. These ATP-competitive KSP inhibitors do not bind in the nucleotide binding pocket. Cumulative data from generation of resistant cells, site-directed mutagenesis and photo-affinity labeling suggest that they compete with ATP binding via a novel allosteric mechanism. 相似文献
50.
Wang J Niemevz F Lad L Huang L Alvarez DE Buldain G Poulos TL de Montellano PR 《The Journal of biological chemistry》2004,279(41):42593-42604
Human heme oxygenase-1 (hHO-1) catalyzes the O2-dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the alpha-meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IXalpha. Surprisingly, a 15-methyl substituent caused exclusive cleavage at the gamma-meso-rather than at the normal, unsubstituted alpha-meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the porphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IXalpha and oxidizes 15-phenylheme at the alpha-meso position to give 10-phenylbiliverdin IXalpha. The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-A crystal structures of the hHO-1 complexes with 1- and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141-150 and in the proximal Lys18 and Lys22. In the 5-phenylheme-hHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26-42 near the alpha-meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity. 相似文献