A monoclonal antibody to the epsilon-aminocaproic acid binding site on the kringle 4 region of human plasminogen that accelerates the activation of Glu1-plasminogen by urokinase.

A monoclonal antibody to the epsilon-aminocaproic acid binding site on the kringle 4 region of human plasminogen that accelerates the activation of Glu1-plasminogen by urokinase.
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一种针对人纤溶酶原 Kringle 4 区域上的 ε-氨基己酸结合位点的单克隆抗体,可加速尿激酶对 Glu1-纤溶酶原的激活。

DOI:
10.1016/0003-9861(85)90665-4
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发表时间:
1985
影响因子:
3.9
通讯作者:
Castellino,FJ
Castellino,FJ
中科院分区:
生物学3区
文献类型:
--
作者:
Cummings,HS;Castellino,FJ

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一种单克隆抗体,10-F-1,以前显示[VA Ploplis,HS Cummings,和FJ Castellino(1982)Biochemistry 21,5891-5897]与人Glu 1-纤溶酶原的kringle 4(K4)区上的特定β-氨基己酸(EACA)3结合位点相互作用(Glu 1-Pg),已被用于评估EACA及其类似物对增强尿激酶(UK)催化的Glu 1-Pg活化的这种特定EACA位点的贡献。与EACA样化合物的情况一样,抗体10-F-1的存在加速了UK对Glu 1-Pg的激活,但不增强对Lys 77-纤溶酶原的类似激活。在使其在Glu 1-Pg上的结合位点饱和的抗体10-F-1的浓度存在下,UK活化Glu 1-Pg的Km从1.4±0.2 μ m(在不存在抗体的情况下获得的值)升高至17.0±2.0 μ m。另一方面,该活化的kcat为0.038±0.005 s-1,在抗体10-F-1的饱和浓度下升高至2.45±0.2 s-1。在这些条件下,在不存在抗体的情况下,活化的k cat Km为0.027 s− 1 μ m− 1,在存在饱和水平的抗体10-F-1的情况下,活化的k cat Km为0.144 s− 1 μ m− 1。这表明该抗体与其表位的相互作用导致UK对Glu 1-Pg的激活速率的五倍刺激。抗体10-F-1的可用性允许探测人纤溶酶原上4至5个代谢上等价的弱EACA位点之一的功能的特异性手段。从这个特定的研究中,可以得出结论,Glu 1-Pg的K4结构域上的EACA弱结合位点部分或全部负责EACA对UK激活人Glu 1-Pg的增强作用。
Abstract A monoclonal antibody, 10-F-1, previously shown [VA Ploplis, HS Cummings, and FJ Castellino (1982) Biochemistry21, 5891–5897] to interact with a particular ϵ-aminocaproic acid (EACA) 3 binding site on the kringle 4 (K4) region of human Glu 1-plasminogen (Glu 1-Pg), has been employed to assess the contribution of this particular EACA site toward the enhancement, by EACA and its analogs, of the urokinase (UK)-catalyzed activation of Glu 1-Pg. As is the case with EACA-like compounds, the presence of antibody 10-F-1 accelerates the activation of Glu 1-Pg by UK, but does not enhance the similar activation of Lys 77-plasminogen. In the presence of concentrations of antibody 10-F-1 which saturate its binding site on Glu 1-Pg, the K m of Glu 1-Pg activation by UK is raised from 1.4±0.2 μ m, a value obtained in the absence of antibody, to 17.0±2.0 μ m On the other hand, the k cat for this activation, 0.038±0.005 s− 1, is elevated to 2.45±0.2 s− 1 at saturating concentrations of antibody 10-F-1. The k cat K m for activation under these conditions is 0.027 s− 1 μ m− 1 in the absence of antibody, and 0.144 s− 1 μ m− 1 in the presence of saturating levels of antibody 10-F-1. This demonstrates that the interaction of this antibody with its epitope results in a fivefold stimulation of the activation rate of Glu 1-Pg by UK. The availability of antibody 10-F-1 allows for a specific means of probing the function of one of the four to five thermodynamically equivalent weak EACA sites on human plasminogen. From this particular study, it is concluded that the weak binding site for EACA on the K4 domain of Glu 1-Pg is either in-part or in-whole responsible for the enhancing effect of EACA on human Glu 1-Pg activation by UK.
ε-氨基己酸对纤溶酶原和纤溶酶总体构象的影响
DOI: --
发表时间: 1975
期刊:
影响因子: --
作者:
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通讯作者: F. Castellino
α-、omega-氨基酸对人纤溶酶原结构和激活的影响。
DOI: --
发表时间: 1978
影响因子: 4.8
作者:
B. Violand;R. Byrne;F. Castellino
通讯作者: F. Castellino
DOI: --
发表时间: 1975
影响因子: 4.8
作者:
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通讯作者: F. Castellino
测量抗纤维蛋白溶解氨基酸与各种纤溶酶原的结合。
DOI: --
发表时间: 1972
影响因子: 3.9
作者:
W. J. Brockway;F. Castellino
通讯作者: F. Castellino
DOI: --
发表时间: 1979
影响因子: 4.8
作者:
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通讯作者: F. Castellino