Kunitz（抑肽酶）型结构同源蛋白酶抑制剂对猪腺体激肽释放酶的抑制作用。抑制位点氨基酸残基碱性性质对激肽释放酶抑制的意义。

Inhibition of porcine glandular kallikreins by structurally homologous proteinase inhibitors of the Kunitz (Trasylol) type. Significance of the basic nature of amino acid residues in subside positions for kallikrein inhibition.

作者信息

Dietl T, Huber C, Geiger R, Iwanaga S, Fritz H

出版信息

Hoppe Seylers Z Physiol Chem. 1979 Jan;360(1):67-71. doi: 10.1515/bchm2.1979.360.1.67.

DOI:10.1515/bchm2.1979.360.1.67

Abstract

The newly synthesized chromogenic substrate D ValLeuArgNHNp was employed to study the inhibition strength of Trasylol-like inhibitors from bovine lung (TKI), sea anemone (SAI), snake venoms (NNV and HHV), snails (HPI) and cow colostrum (CTI) against porcine pancreatic, submandibular and urinary kallikreins. The dissociation constants of the corresponding kallikrein-inhibitor complexes were found close to Ki = 1.5 x 10(-9)M (TKI, SAI, NNV) or to Ki = 10--210 x 10(-9)M (HHV, HPI). CTI does not inhibit the three porcine glandular kallikreins. Comparison of the inhibitory active areas of the inhibitors with their affinities to the three kallikreins shows that kallikrein inhibition is observed only if basic amino acid residues are present in distinct positions of the inhibitory active sites.

摘要

利用新合成的显色底物D-缬氨酸-亮氨酸-精氨酸-对硝基苯胺（D ValLeuArgNHNp）研究了来自牛肺的抑肽酶样抑制剂（TKI）、海葵抑制剂（SAI）、蛇毒（NNV和HHV）、蜗牛抑制剂（HPI）和牛初乳抑制剂（CTI）对猪胰激肽释放酶、颌下腺激肽释放酶和尿激肽释放酶的抑制强度。发现相应激肽释放酶-抑制剂复合物的解离常数接近Ki = 1.5×10⁻⁹M（TKI、SAI、NNV）或Ki = 10⁻²¹⁰×10⁻⁹M（HHV、HPI）。CTI不抑制三种猪腺激肽释放酶。将抑制剂的抑制活性区域与其对三种激肽释放酶的亲和力进行比较，结果表明，只有当抑制活性位点的不同位置存在碱性氨基酸残基时，才会观察到激肽释放酶抑制作用。