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The ends of tropomyosin are major determinants of actin affinity and myosin subfragment 1-induced binding to F-actin in the open state

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BIOCHEMISTRY 1999年第48期38卷 15885-15892页

作者： Moraczewska, J Nicholson-Flynn, K Hitchcock-DeGregori, SE Univ Med & Dent New Jersey Robert Wood Johnson Med Sch Dept Neurosci & Cell Biol Piscataway NJ 08854 USA

Tropomyosin (TM) is thought to exist in equilibrium between two states on F-actin, closed and open [Geeves, M. A., and Lehrer, S. S. (1994) Biophys. J. 67, 273-282]. Myosin shifts the equilibrium to the open state in which myosin binds strongly and develops force. Tropomyosin isoforms, that primarily differ in their N- and C-terminal sequences, have different equilibria between the closed and open states. The aim of the research is to understand how the alternate ends of TM affect cooperative actin binding and the relationship between actin affinity and the cooperativity with which myosin S1 promotes binding of TM to actin in the open state. A series of rat alpha-tropomyosin variants was expressed in Escherichia coli that are identical except for the ends, which are encoded by exons la or Ib and exons 9a, 9c or 9d. Both the N- and C-terminal sequences, and the particular combination within a TM molecule, determine actin affinity. Compared to tropomyosins with an exon la-encoded N-terminus, found in long isoforms, the exon Ib-encoded sequence, expressed in 247-residue nonmuscle tropomyosins, increases actin affinity in tropomyosins expressing 9a or 9d but has little effect with 9c, a brain-specific exon. The relative actin affinities, in decreasing order, are 1b9d > 1b9a, acetylated 1a9a > 1a9d much greater than 1a9a greater than or equal to 1a9c congruent to 1b9c. Myosin S1 greatly increases the affinity of all tropomyosin variants for actin. In this, the actin affinity is the primary factor in the cooperativity with which myosin S1 induces TM binding to actin in the open state;generally, the higher the actin affinity, the lower the occupancy by myosin required to saturate the actin with tropomyosin: 1b9d > 1a9d > 1b9a greater than or equal to acetylated 1a9a > 1a9a > la9c congruent to 1b9c.

关键词：肌动蛋白类/化学氨基酸序列鸡 DNA 互补/代谢大肠杆菌/遗传学大肠杆菌/代谢基因表达分子序列数据肌球蛋白亚碎片/药理学肌球蛋白类/药理学蛋白质结合/药物作用蛋白质构象蛋白质折叠原肌球蛋白/生物合成原肌球蛋白/化学原肌球蛋白/遗传学肌钙蛋白/化学动物大鼠

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Prenyl-flavonoids as potent inhibitors of the Pdr5p multidrug ABC transporter from Saccharomyces cerevisiae

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BIOCHEMISTRY 2000年第23期39卷 6910-6917页

作者： Conseil, G Decottignies, A Jault, JM Comte, G Barron, D Goffeau, A Di Pietro, A CNRS UPR 412 Inst Biol & Chim Prot Lab Biochim Struct & Fonctionnelle F-69367 Lyon 07 France Univ Catholique Louvain Unite Biochim Physiol B-1348 Louvain Belgium Univ Lyon 1 UPRESA 5013 Lab Prod Nat F-69622 Villeurbanne France

The Pdr5p multidrug ABC ("ATP-binding cassette") transporter was highly overexpressed in plasma membranes from a yeast strain exhibiting both pdr1-3 gain-of-function mutation in the transcription factor-encoding gene PDR1 and disruption of genes encoding other plasma membrane ABC transporters. Solubilized and purified PdrSp displayed a tryptophan-characteristic intrinsic fluorescence, whose quenching was used to monitor interactions with substrates and effecters. The transporter exhibited a magnesium-dependent binding affinity for ATP and its fluorescent analogue 2'(3')-N-methylanthraniloyl-ATP, producing a marked fluorescence resonance-energy transfer. It also bound a series of known drug substrates and modulators. Interestingly, yeast PdrSp interacted with flavonoids recently found to bind to cancer cell P-glycoprotein and to the protozoan parasite multidrug transporter. The extent of high-affinity binding of prenyl-flavonoids to purified PdrSp was correlated to their efficiency to inhibit energy-dependent quenching of rhodamine 6G fluorescence catalyzed by Pdr5p-enriched plasma membranes. The hydrophobic flavonoid derivative 6-(3,3-dimethylallyl)galangin was the most efficient, with a K-i of 0.18 mu M for competitive inhibition of the MgATP-dependent quenching of rhodamine 6G fluorescence. In contrast, inhibition of either ATP or UTP hydrolysis occurred at much higher concentrations and appeared to be noncompetitive, Prenyl-flavonoids therefore behave as potent inhibitors of drug binding to the yeast PdrSp ABC transporter.

关键词： ATP结合匣式转运子/拮抗剂和抑制剂 ATP结合匣式转运子/代谢腺苷三磷酸酶类/代谢腺苷三磷酸/类似物和衍生物腺苷三磷酸/代谢 DNA结合蛋白质类/遗传学酶抑制剂/药理学类黄酮物质/药理学真菌蛋白质类/拮抗剂和抑制剂真菌蛋白质类/代谢动力学镁/药理学膜蛋白质类/拮抗剂和抑制剂膜蛋白质类/代谢分子结构蛋白质结合/药物作用焦磷酸酶类/代谢若丹明类酿酒酵母菌/药物作用酿酒酵母菌/遗传学酿酒酵母蛋白质类光谱法荧光底物特异性反式激活因子类/遗传学转录因子色氨酸/化学

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Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第41期275卷 31682-31688页

作者： Kang, J Kim, T Ko, YG Rho, SB Park, SG Kim, MJ Kwon, HJ Kim, S Sungkyunkwan Univ Ctr ARS Network Natl Creat Res Initiat Ctr Jangan Gu Suwon 440746 Kyunggido South Korea Sejong Univ Dept Biosci & Biotechnol Kwangjin Gu Seoul 143747 South Korea

Heat shock protein 90 (hsp90) is a molecular chaperone responsible for protein folding and maturation in vivo. Interaction of hsp90 with human glutamyl-prolyl-tRNA synthetase (EPRS) was found by genetic screening, co-immunoprecipitation, and in vitro binding experiments. This interaction was sensitive to the hsp90 inhibitor, geldanamycin, and also ATP, suggesting that the chaperone activity of hsp90 is required for interaction with EPRS. Interaction of EPRS with hsp90 was targeted to the region of three tandem repeats linking the two catalytic domains of EPRS that is also responsible for the interaction with isoleucyl-tRNA synthetase (IRS), Interaction of EPRS and IRS also depended on the activity of hsp90, implying that their association was mediated by hsp90. EPRS and IRS form a macromolecular protein complex with at least six other tRNA synthetases and three cofactors, hsp90 preferentially binds to most of the complex-forming enzymes rather than those that are not found in the complex. In addition, inactivation of hsp90 interfered with the in vivo incorporation of the nascent aminoacyl-tRNA synthetases into the multi-ARS complex. Thus, hsp90 appears to mediate protein-protein interactions of mammalian tRNA synthetases.

关键词：腺苷三磷酸/代谢腺苷三磷酸/药理学氨酰基tRNA合成酶类/拮抗剂和抑制剂氨酰基tRNA合成酶类/代谢苯醌类结合部位 HSP90热休克蛋白质类/拮抗剂和抑制剂 HSP90热休克蛋白质类/代谢 HeLa细胞羟肟酸类/药理学内酰胺类大环内酯类/药理学大环内酯类大分子物质沉淀素试验蛋白质结合/药物作用醌类/药理学底物特异性串联重复序列双杂交系统技术酵母菌动物牛人类

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Tissue factor pathway inhibitor binds to platelet thrombospondin-1

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第41期275卷 31715-31721页

作者： Mast, AE Stadanlick, JE Lockett, JM Dietzen, DJ Hasty, KA Hall, CL Univ Tennessee Res Serv Dept Vet Affairs Memphis TN 38104 USA Univ Tennessee Pathol Serv Dept Vet Affairs Memphis TN 38104 USA Univ Tennessee Dept Pathol Memphis TN 38104 USA Univ Tennessee Dept Anat Memphis TN 38104 USA Univ Memphis Dept Biomed Engn Memphis TN 38152 USA

Tissue factor pathway inhibitor (TFPI) is a Kunitz-type serine proteinase inhibitor that down-regulates tissue factor-initiated blood coagulation. The most biologically active pool of TFPI is associated with the vascular endothelium, however, the biochemical mechanisms responsible for its cellular binding are not entirely defined. Proposed cellular binding sites for TFPI include nonspecific association with cell surface glycosaminoglycans and binding to glycosyl phosphatidylinositol-anchored proteins. Here, we report that TFPI binds specifically and saturably to thrombospondin-l (TSP-1) purified from platelet alpha-granules with an apparent K-D of similar to 7.5 nM. Binding is inhibited by polyclonal antibodies against TFPI and partially inhibited by the B-7 monoclonal anti-TSP-l antibody. TFPI bound to immobilized TSP-1 remains an active proteinase inhibitor. Additionally, in solution phase assays measuring TFPI inhibition of factor VIIa/tissue factor catalytic activity, the rate of factor Xa generation was decreased 55% in the presence of TSP-1 compared with TFPI alone. Binding experiments done in the presence of heparin and with altered forms of TFPI suggest that the basic C-terminal region of TFPI is required for TSP-1 binding. The data provide a mechanism for the recruitment and localization of TFPI to extravascular surfaces within a bleeding wound, where it can efficiently down-regulate the procoagulant activity of tissue factor and allow subsequent aspects of platelet-mediated healing to proceed.

关键词：抗体/药理学结合部位血液凝固/生理学血小板/化学血小板/细胞学催化作用细胞质颗粒/化学减量调节因子Ⅶa/拮抗剂和抑制剂因子Ⅶa/代谢因子Ⅹa/拮抗剂和抑制剂因子Ⅹa/代谢肝素/药理学动力学脂蛋白类/化学脂蛋白类/遗传学脂蛋白类/免疫学脂蛋白类/代谢突变蛋白质结合/药物作用蛋白质结构三级重组蛋白质类/遗传学重组蛋白质类/代谢丝氨酸蛋白酶抑制剂/化学丝氨酸蛋白酶抑制剂/遗传学丝氨酸蛋白酶抑制剂/免疫学丝氨酸蛋白酶抑制剂/代谢底物特异性凝血酶敏感蛋白1/免疫学凝血酶敏感蛋白1/代谢人类

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Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability

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JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第24期274卷 17318-17324页

作者： Henics, T Nagy, E Oh, HJ Csermely, P von Gabain, A Subjeck, JR Vienna Bioctr Inst Microbiol & Genet A-1030 Vienna Austria Univ Pecs Sch Med Dept Med Microbiol & Immunol H-7643 Pecs Hungary Univ Pecs Sch Med Dept Clin Biochem H-7643 Pecs Hungary Roswell Pk Canc Inst Dept Mol & Cellular Biol Buffalo NY 14263 USA Semmelweis Univ Dept Med Chem H-1444 Budapest 8 Hungary

In this study, in vitro RNA binding by members of the mammalian 70-kDa heat shock protein (Hsp) family was examined. We show that Hsp/Hsc70 and Hsp110 proteins preferentially bound AU-rich RNA in vitro. Inhibition of RNA binding by ATP suggested the involvement of the N-terminal ATP-binding domain, By using deletion mutants of Hsp110 protein, a diverged Hsp70 family member, RNA binding was localized to the N-terminal ATP-binding domain of the molecule. The C-terminal peptide-binding domain did not bind RNA, but its engagement by a peptide substrate abrogated RNA binding by the N terminus of the protein. Interestingly, removal of the C-terminal alpha-helical structure or the alpha-loop domain unique to Hsp110 immediately downstream of the peptide-binding domain, but not both, resulted in considerably increased RNA binding as compared with the wild type protein. Finally, a 70 kDa activity was immunoprecipitated from RNA-protein complexes formed in vitro between cytoplasmic proteins of human lymphocytes and AU-rich RNA. These findings support the idea that certain heat shock proteins may act as RNA-binding entities in vivo to guide the appropriate folding of RNA substrates for subsequent regulatory processes such as mRNA degradation and/or translation.

关键词： 3'非翻译区腺苷三磷酸/药理学碱基组成碱基序列结合部位载体蛋白质类/代谢 HSC70热休克蛋白质类 HSP110热休克蛋白质类 HSP70热休克蛋白质类/遗传学 HSP70热休克蛋白质类/代谢乳清蛋白分子序列数据突变沉淀素试验蛋白质结合/药物作用 RNA 信使/代谢 RNA结合蛋白质类/代谢序列缺失

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Crystal structure of a conformation-selective casein kinase-1 inhibitor

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第26期275卷 20052-20060页

作者： Mashhoon, N DeMaggio, AJ Tereshko, V Bergmeier, SC Egli, R Hoekstra, MF Kuret, J Ohio State Univ Coll Med Sch Med Ctr BiotechnolDept Med Biochem Columbus OH 43210 USA ICOS Corp Bothell WA 98021 USA Northwestern Univ Sch Med Dept Biol Chem & Mol Pharmacol Chicago IL 60611 USA Ohio State Univ Coll Pharm Div Med Chem Columbus OH 43210 USA

Members of the casein kinase-1 family of protein kinases play an essential role in cell regulation and disease pathogenesis. Unlike most protein kinases, they appear to function as constitutively active enzymes. As a result, selective pharmacological inhibitors can play an important role in dissection of casein kinase-1-dependent processes. To address this need, new small molecule inhibitors of casein kinase-1 acting through ATP-competitive and ATP-noncompetitive mechanisms were isolated on the basis of in vitro screening. Here we report the crystal structure of 3-[(2,4,6-trimethoxyphenyl) methylidenyl]-indolin-2-one (IC261), an ATP-competitive inhibitor with differential activity among casein kinase-1 isoforms, in complex with the catalytic domain of fission yeast casein kinase-1 refined to a crystallographic R-factor of 22.4% at 2.8 Angstrom resolution. The structure reveals that IC261 stabilizes casein kinase-1 in a conformation midway between nucleotide substrate liganded and nonliganded conformations. We propose that adoption of this conformation by casein kinase-1 family members stabilizes a delocalized network of side chain interactions and results in a decreased dissociation rate of inhibitor.

关键词：酪蛋白激酶类计算机模拟结晶学 X线静电学酶抑制剂/药理学氢键合吲哚类/化学吲哚类/药理学半数抑制浓度动力学模型分子分子序列数据突变肽库间苯三酚/类似物和衍生物间苯三酚/化学间苯三酚/药理学磷酸转移酶类/代谢蛋白质结合/药物作用蛋白质构象/药物作用蛋白质亚型/化学蛋白激酶抑制剂蛋白质结构三级裂殖酵母菌属/酶学人类

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Cytoplasmic dynein ATPase activity is regulated by dynactin-dependent phosphorylation

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第41期275卷 31798-31804页

作者： Kumar, S Lee, IH Plamann, M Univ Missouri Sch Biol Sci Kansas City MO 64110 USA

Cytoplasmic dynein is a microtubule-associated motor that utilizes ATP hydrolysis to conduct minus-end directed transport of various organelles. Dynactin is a multisubunit complex that has been proposed to both link dynein with cargo and activate dynein motor function. The mechanisms by which dynactin regulates dynein activity are not clear. In this study, we examine the role of dynactin in regulating dynein ATPase activity. We show that dynein-microtubule binding and ATP-dependent release of dynein from microtubules are reduced in dynactin null mutants, Delta ro-3 (p150(Glued)) and Delta ro-4 (Arp1), relative to wild-type. The dynein-microtubule binding activity, but not the ATP-dependent release of dynein from microtubules, is restored by in vitro mixing of extracts from dynein and dynactin mutants. Dynein produced in a Delta ro-3 mutant has similar to 8-fold reduced ATPase activity relative to dynein isolated from wildtype. However, dynein ATPase activity from wild-type is not reduced when dynactin is separated from dynein, suggesting that dynein produced in a dynactin mutant is inactivated. Treatment of dynein isolated from the Delta ro-3 mutant with lambda protein phosphatase restores the ATPase activity to near wild-type levels. The reduced dynein ATPase activity observed in dynactin null mutants is mainly due to altered affinity for ATP. Radiolabeling experiments revealed that low molecular mass proteins, particularly 20- and 8-kDa proteins, that immunoprecipitate with dynein heavy chain are hyperphosphorylated in the dynactin mutant and dephosphorylated upon A protein phosphatase treatment. The results suggest that cytoplasmic dynein ATPase activity is regulated by dynactin-dependent phosphorylation of dynein light chains.

关键词：腺苷三磷酸/代谢腺苷三磷酸/药理学脑离心法梯密度细胞质/酶学细胞质/代谢动力蛋白ATP酶/遗传学动力蛋白ATP酶/代谢酶激活真菌蛋白质类/遗传学真菌蛋白质类/代谢动力学微管相关蛋白质类/遗传学微管相关蛋白质类/代谢微管/代谢分子序列数据分子量突变链孢霉粗糙/酶学链孢霉粗糙/遗传学磷酰化沉淀素试验蛋白质结合/药物作用动物牛

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A binding site for the kringle II domain of prothrombin in the Apple 1 domain of factor XI

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第41期275卷 31954-31962页

作者： Baglia, FA Badellino, KO Ho, DH Dasari, VR Walsh, PN Temple Univ Sch Med Sol Sherry Thrombosis Res Ctr Philadelphia PA 19140 USA Temple Univ Sch Med Dept Med Philadelphia PA 19140 USA Temple Univ Sch Med Dept Biochem Philadelphia PA 19140 USA NCI Med Branch NIH Bethesda MD 20892 USA

Previously we defined binding sites for high molecular weight kininogen (HK) and thrombin in the Apple 1 (Al) domain of factor XI (FM). Since prothrombin (and Ca2+) can bind FXI and can substitute for HK (and Zn2+) as a cofactor for FXI binding to platelets, we have attempted to identify a prothrombin-binding site in FXI. The recombinant Al domain (rAl, Glu(1)-Ser(90)) inhibited the saturable, specific and reversible binding of prothrombin to FXI, whereas neither the rA2 domain (Ser(90)-Ala(181)), rA3 domain (Ala(181)-Val(271)), nor rA4 domain (Phe(272)-Glu(361)) inhibited prothrombin binding to FXI. Kinetic binding studies using surface plasmon resonance showed binding of FXI (K-d similar to 71 nn) and the rAl domain (K-d similar to 239 nM) but not rA2, rA3, or rA4 to immobilized prothrombin. Reciprocal binding studies revealed that synthetic peptides (encompassing residues Ala(45)-Ser(86)) containing both HK- and thrombin-binding sites, inhibit I-125-rAl (Glu(1)-Ser(90)) binding to prothrombin, I-125-prothrombin binding to FXI, and 125I-prothrombin fragment 2 (Ser(156)-Arg(271)) binding to FXI. However, homologous prekallikrein-derived peptides (encompassing Pro(45)-Gly(86)) did not inhibit FXI rAl binding to prothrombin. The peptides Ala(45)-Arg(54), Phe(56)-Val(71), and Asp(72)-Ser(86), derived from sequences of the Al domain of FXI, acted synergistically to inhibit I-125-rAl binding to prothrombin. Mutant rAl peptides (V64A and I77A), which did not inhibit FXI binding to III, retained full capacity to inhibit rAl domain binding to prothrombin, and mutant rAl peptides Ala(45)-Ala(54) (D51A) and Val(59)-Arg(70) (E66A), which did not inhibit FXI binding to thrombin, retained full capacity to inhibit rAl domain binding to prothrombin. Thus, these experiments demonstrate that a prothrombin binding site exists in the Al domain of FXI spanning residues Ala(45)-Ser(86) that is contiguous with but separate and distinct from the HK- and thrombin-binding sites and that th

关键词：结合部位结合竞争性因子Ⅺ/化学因子Ⅺ/遗传学因子Ⅺ/代谢碘放射性同位素动力学激肽原高分子量/代谢带双硫键三环蛋白结构区肽碎片/代谢肽碎片/药理学蛋白质结合/药物作用凝血酶原/化学凝血酶原/代谢重组蛋白质类/化学重组蛋白质类/遗传学重组蛋白质类/代谢表面等离激元凝血酶/代谢人类

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Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae - eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第41期275卷 32363-32370页

作者： Igarashi, J Michel, T Harvard Univ Brigham & Womens Hosp Div Cardiovasc Sch Med Boston MA 02115 USA Vet Affairs Boston Healthcare Syst W Roxbury MA 02132 USA

Plasmalemmal caveolae are membrane microdomains that are specifically enriched in sphingolipids and contain a wide array of signaling proteins, including the endothelial isoform of nitric-oxide synthase (eNOS). EDG-1 is a G protein-coupled receptor for sphingosine 1-phosphate (S1P) that is expressed in endothelial cells and has been implicated in diverse vascular signal transduction pathways. We analyzed the subcellular distribution of EDG-1 in COS-7 cells transiently transfected with cDNA constructs encoding epitope-tagged EDG-1. Subcellular fractionation of cell lysates resolved by ultracentrifugation in discontinuous sucrose gradients revealed that similar to 55% of the EDG-1 protein was recovered in fractions enriched in caveolin-1, a resident protein of caveolae, Co-immunoprecipitation experiments showed that EDG-1 could be specifically precipitated by antibodies directed against caveolin-1 and vice versa. The targeting of EDG-1 to caveolae-enriched fractions was markedly increased (from 51 +/- 11% to 93 +/- 14%) by treatment of transfected cells with S1P (5 mu M, 60 min). In co-transfection experiments expressing EDG-1 and eNOS cDNAs in COS-7 cells, we found that S1P treatment significantly and specifically increased nitric-oxide synthase activity, with an EC50 of 30 nM S1P. Overexpression of transfected caveolin-1 cDNA together with EDG-1 and eNOS markedly diminished S1P-mediated eNOS activation;caveolin overexpression also attenuated agonist-induced phosphorylation of EDG-1 receptor by >90%. These results suggest that the interaction of the EDG-1 receptor with caveolin may serve to inhibit signaling through the S1P pathway, even as the targeting of EDG-1 to caveolae facilitates the interactions of this receptor with ligands and effecters that are also targeted to caveolae. The agonist-modulated targeting of EDG-1 to caveolae and its dynamic inhibitory interactions with caveolin identify new points for regulation of sphingolipid-dependent signaling in the vas

关键词：溶血磷脂素类一氧化氮/代谢一氧化氮合酶/代谢磷酰化/药物作用沉淀素试验蛋白质结合/药物作用蛋白质转运/药物作用受体细胞表面受体 G-蛋白偶联受体溶血磷脂重组融合蛋白质类/代谢信号传导/药物作用鞘氨醇/类似物和衍生物鞘氨醇/拮抗剂和抑制剂鞘氨醇/药理学转染

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Lipid-dependent activation of protein kinase C-α by normal alcohols

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JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第48期274卷 34036-34044页

作者： Shen, YMA Chertihin, OI Biltonen, RL Sando, JJ Univ Virginia Hlth Sci Ctr Dept Pharmacol Charlottesville VA 22903 USA Univ Virginia Hlth Sci Ctr Biophys Program Charlottesville VA 22903 USA Univ Virginia Hlth Sci Ctr Ctr Canc Charlottesville VA 22903 USA

Significant stimulation of protein kinase C-alpha (PKC alpha) by n-alcohols was observed in characterized lipid systems composed of phosphatidylcholine/phosphatidylserine/dioleoylglycerol (PC/PS/DO), The logarithm of the alcohol concentrations to achieve half-maximal PKC stimulation (ED50) and of the maximal PKC stimulation by alcohols were both linear functions of alcohol chain length, consistent with the Meyer-Overton effect. Binding of phorbol esters to PKC was not significantly affected by octanol, Octanol increased, up to 4-fold, the affinity of PKC binding to the lipid bilayers in both the absence and presence of DO. However, octanol increased PKC activity much more significantly than it enhanced binding of the enzyme to the lipid bilayers, suggesting that the stimulation of PKC is not merely a reflection of the increase in PKC bilayer binding affinity. P-31 NMR experiments did not reveal formation of non-lamellar phases with octanol, Differential scanning calorimetry suggested that alcohols, like diacylglycerol, induce formation of compositionally distinct domains and the maximal enzyme activity with alcohol resided roughly in the putative domain-coexistence region. These results suggest that alcohols are mimicking diacylglycerol in activating PKC, not by binding to the high affinity phorbol ester binding site, but by altering lipid structure and by enhancing PCK-bilayer binding.

关键词：醇类/化学醇类/药理学结合竞争性/药物作用甘油二酯类/化学二肉豆蔻磷脂酰胆碱/化学剂量效应关系药物酶激活/药物作用同工酶类/化学同工酶类/代谢脂双层/化学脂双层/代谢脂类/化学膜流动性辛醇类/药理学戊醇类/药理学佛波醇酯类/代谢磷脂酰丝氨酸类/化学蛋白质结合/药物作用蛋白激酶C/化学蛋白激酶C/代谢蛋白激酶Cα 温度

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