微管蛋白的聚合与解聚：由两个不同的长春花碱结合位点介导
Tubulin aggregation and disaggregation: mediation by two distinct vinblastine-binding sites.
作者信息
Bhattacharyya B, Wolff J
出版信息
Proc Natl Acad Sci U S A. 1976 Jul;73(7):2375-8. doi: 10.1073/pnas.73.7.2375.
Abstract
Rat brain tubulin possesses two distinct binding sites for vinblastine per molecule: a high-affinity site with an affinity constant of 6.2 x 10(6) M-1 and a low-affinity site with an affinity constant of 8 x 10(4) M-1. The high-affinity site is labile, with a t1/237 degrees of 3.5 hr, is protected by colchicine, and is unaffected by salt, whereas the low-affinity site is stable but is inhibited by salt. Binding to both sites is rapid. The high-affinity binding constant of vinblastine to tubulin (6.2 x 10(6) M-1) corresponds to the half-maximal concentration of vinblastine needed to prevent polymerization of tubulin in vitro, whereas the low-affinity binding constant (8 x 10(4) M-1) corresponds to the half-maximal concentration of vinblastine required to aggregate tubulin. We conclude that vinblastine binding to the high- and low-affinity sites, respectively, accounts for the depolymerization and aggregation behavior of tubulin.
摘要
大鼠脑微管蛋白每个分子具有两个不同的长春花碱结合位点
一个高亲和力位点，亲和常数为6.2×10⁶ M⁻¹，一个低亲和力位点，亲和常数为8×10⁴ M⁻¹。高亲和力位点不稳定，37℃时的半衰期为3.5小时，受秋水仙碱保护，不受盐的影响，而低亲和力位点稳定但受盐抑制。与两个位点的结合都很快。长春花碱与微管蛋白的高亲和力结合常数（6.2×10⁶ M⁻¹）对应于体外防止微管蛋白聚合所需的长春花碱半最大浓度，而低亲和力结合常数（8×10⁴ M⁻¹）对应于聚集微管蛋白所需的长春花碱半最大浓度。我们得出结论，长春花碱分别与高亲和力和低亲和力位点的结合解释了微管蛋白的解聚和聚集行为。
相似文献
1
Tubulin aggregation and disaggregation: mediation by two distinct vinblastine-binding sites.微管蛋白的聚合与解聚：由两个不同的长春花碱结合位点介导
Proc Natl Acad Sci U S A. 1976 Jul;73(7):2375-8. doi: 10.1073/pnas.73.7.2375.
2
The mechanism of action of vinblastine. Binding of [acetyl-3H]vinblastine to embryonic chick brain tubulin and tubulin from sea urchin sperm tail outer doublet microtubules.长春碱的作用机制。[乙酰基-3H]长春碱与鸡胚脑微管蛋白以及海胆精子尾部外侧双联体微管微管蛋白的结合。
Biochemistry. 1975 Dec 30;14(26):5586-92. doi: 10.1021/bi00697a008.
3
Direct photoaffinity labeling of tubulin with colchicine.用秋水仙碱对微管蛋白进行直接光亲和标记。
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2820-4. doi: 10.1073/pnas.88.7.2820.
4
Colchicine-binding protein of the liver. Its characterization and relation to microtubules.肝脏的秋水仙碱结合蛋白。其特性及与微管的关系。
J Cell Biol. 1975 Sep;66(3):609-20. doi: 10.1083/jcb.66.3.609.
5
Membrane-bound tubulin in brain and thyroid tissue.脑和甲状腺组织中的膜结合微管蛋白。
J Biol Chem. 1975 Oct 10;250(19):7639-46.
6
Analysis of drug-tubulin interaction by trypsin cleavage: comparison for colchicine, podophyllotoxin, griseofulvin, vinblastine and taxol.通过胰蛋白酶裂解分析药物与微管蛋白的相互作用：秋水仙碱、鬼臼毒素、灰黄霉素、长春碱和紫杉醇的比较
Comp Biochem Physiol B. 1986;85(3):635-8. doi: 10.1016/0305-0491(86)90060-x.
7
Evaluation of the cytotoxic mechanism mediated by baccatin III, the synthetic precursor of taxol.对紫杉醇的合成前体浆果赤霉素III介导的细胞毒性机制的评估。
Chem Biol Interact. 1996 Aug 14;101(2):103-14. doi: 10.1016/0009-2797(96)03713-1.
8
Podophyllotoxin as a probe for the colchicine binding site of tubulin.鬼臼毒素作为微管蛋白秋水仙碱结合位点的探针。
J Biol Chem. 1977 Feb 25;252(4):1134-40.
9
Interaction of phomopsin A with porcine brain tubulin. Inhibition of tubulin polymerization and binding at a rhizoxin binding site.腐马素A与猪脑微管蛋白的相互作用。在根赤壳菌素结合位点对微管蛋白聚合和结合的抑制作用。
Biochem Pharmacol. 1992 Jan 22;43(2):219-24. doi: 10.1016/0006-2952(92)90281-m.
10
Evidence for involvement of microtubules in the action of vasopressin in toad urinary bladder. II. Colchicine binding properties of toad bladder epithelial cell tubulin.微管参与蟾蜍膀胱中血管加压素作用的证据。II. 蟾蜍膀胱上皮细胞微管蛋白的秋水仙碱结合特性。
J Membr Biol. 1978 May 3;40(3):237-50. doi: 10.1007/BF02002970.
引用本文的文献
1
Ultrapotent vinblastines in which added molecular complexity further disrupts the target tubulin dimer-dimer interface.超效长春碱类药物，其中增加的分子复杂性进一步破坏了靶微管蛋白二聚体-二聚体界面。
Proc Natl Acad Sci U S A. 2016 Aug 30;113(35):9691-8. doi: 10.1073/pnas.1611405113. Epub 2016 Aug 10.
2
Ansamitocin P3 depolymerizes microtubules and induces apoptosis by binding to tubulin at the vinblastine site.安丝菌素 P3 通过与长春碱结合位点结合微管蛋白解聚微管并诱导细胞凋亡。
PLoS One. 2013 Oct 4;8(10):e75182. doi: 10.1371/journal.pone.0075182. eCollection 2013.
3
Antimicrotubular drugs binding to vinca domain of tubulin.抗微管药物与微管蛋白的长春花结构域结合。
Mol Cell Biochem. 2003 Nov;253(1-2):41-7. doi: 10.1023/a:1026045100219.
4
Sodium current modulation by a tubulin/GTP coupled process in rat neonatal cardiac myocytes.大鼠新生心肌细胞中微管蛋白/鸟苷三磷酸（GTP）偶联过程对钠电流的调节作用
J Physiol. 2002 Apr 1;540(Pt 1):93-103. doi: 10.1113/jphysiol.2001.013474.
5
Properties of the kinetochore in vitro. I. Microtubule nucleation and tubulin binding.体外动粒的特性。I. 微管成核作用与微管蛋白结合。
J Cell Biol. 1985 Sep;101(3):755-65. doi: 10.1083/jcb.101.3.755.
6
Differential in vitro action of S-12363, a new vinblastine derivative, and of its epimer on microtubule proteins.新型长春碱衍生物S-12363及其差向异构体对微管蛋白的体外差异作用
Cancer Chemother Pharmacol. 1991;28(6):434-40. doi: 10.1007/BF00685819.
7
Interaction of the tumor inhibitor IKP-104, a 4(1H)-pyridinone derivative, with microtubule proteins.肿瘤抑制剂IKP-104（一种4(1H)-吡啶酮衍生物）与微管蛋白的相互作用。
Jpn J Cancer Res. 1992 Feb;83(2):211-8. doi: 10.1111/j.1349-7006.1992.tb00088.x.
8
The current and future place of vinorelbine in cancer therapy.长春瑞滨在癌症治疗中的当前及未来地位。
Drugs. 1992;44 Suppl 4:36-45; discussion 66-9. doi: 10.2165/00003495-199200444-00005.
9
Interaction of vinblastine analogues with tubulin.长春碱类似物与微管蛋白的相互作用。
Experientia. 1978 Nov 15;34(11):1479-9. doi: 10.1007/BF01932374.
10
Induction of paracrystalline arrays by vincristine in the synaptic formations of the teleost retina.长春新碱在硬骨鱼视网膜突触结构中诱导副晶状阵列的形成。
Cell Tissue Res. 1978 Jul 13;191(1):75-82. doi: 10.1007/BF00223216.
本文引用的文献
1
Protein measurement with the Folin phenol reagent.使用福林酚试剂进行蛋白质测定。
J Biol Chem. 1951 Nov;193(1):265-75.
2
The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis.通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳测定分子量的可靠性。
J Biol Chem. 1969 Aug 25;244(16):4406-12.
3
Microtubular crystals in mammalian cells.哺乳动物细胞中的微管晶体。
J Cell Biol. 1969 Jan;40(1):95-107. doi: 10.1083/jcb.40.1.95.
4
The colchicine-binding protein of mammalian brain and its relation to microtubules.哺乳动物脑内的秋水仙碱结合蛋白及其与微管的关系。
Biochemistry. 1968 Dec;7(12):4466-79. doi: 10.1021/bi00852a043.
5
Properties of colchicine binding protein from chick embryo brain. Interactions with vinca alkaloids and podophyllotoxin.鸡胚脑秋水仙碱结合蛋白的特性。与长春花生物碱和鬼臼毒素的相互作用。
Biochemistry. 1970 Dec 8;9(25):4999-5007. doi: 10.1021/bi00827a026.
6
Aggregation of microtubule subunit protein. Effects of divalent cations, colchicine and vinblastine.微管亚基蛋白的聚合。二价阳离子、秋水仙碱和长春花碱的作用。
Biochemistry. 1970 Oct 13;9(21):4110-6. doi: 10.1021/bi00823a012.
7
Structure of microtubular crystals induced by vinblastine in vitro.长春碱在体外诱导形成的微管晶体的结构
J Cell Biol. 1970 Jan;44(1):234-8. doi: 10.1083/jcb.44.1.234.
8
A circular dichroism study of microtubule protein.微管蛋白的圆二色性研究。
Biochemistry. 1972 Apr 25;11(9):1554-61.
9
The binding of vincristine, vinblastine and colchicine to tubulin.长春新碱、长春碱和秋水仙碱与微管蛋白的结合。
Biochem Biophys Res Commun. 1972 May 26;47(4):685-91. doi: 10.1016/0006-291x(72)90546-3.
10
Interaction of drugs with microtubule proteins.药物与微管蛋白的相互作用。
Fed Proc. 1974 Feb;33(2):158-66.
Zotero 插件