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膜型基质金属蛋白酶-1（MT1-MMP）的重组催化结构域可诱导前明胶酶A以及与组织金属蛋白酶抑制剂-2（TIMP-2）复合的前明胶酶A的激活。

The recombinant catalytic domain of membrane-type matrix metalloproteinase-1 (MT1-MMP) induces activation of progelatinase A and progelatinase A complexed with TIMP-2.

作者信息

Lichte A, Kolkenbrock H, Tschesche H

机构信息

Universität Bielefeld, Fakultät für Chemie, Abteilung Biochemie I, Bielefeld, Germany.

出版信息

FEBS Lett. 1996 Nov 18;397(2-3):277-82. doi: 10.1016/s0014-5793(96)01206-9.

DOI:10.1016/s0014-5793(96)01206-9
PMID:8955363
Abstract

A truncated form of the membrane-type matrix metalloproteinase-1 [(Ala21-Ile318)proMT1-MMP] lacking the hemopexin-like and trans-membrane domain was produced in E. coli. We demonstrate that the recombinant proenzyme was autoproteolytically processed to a fully active catalytic domain with N-terminal Ile114. The catalytic domain of MT1-MMP initiated the activation of progelatinase A and progelatinase A complexed with tissue inhibitor of metalloproteinases-2 (TIMP-2). As a typical soluble metalloproteinase it was able to cleave physiologic as well as synthetic substrates. Our kinetic data demonstrate that TIMP-2 is a potent inhibitor for the recombinant enzyme.

摘要

在大肠杆菌中产生了一种截短形式的膜型基质金属蛋白酶-1[（Ala21-Ile318）proMT1-MMP]，其缺乏类血红素结合蛋白样结构域和跨膜结构域。我们证明重组酶原可通过自身蛋白水解加工成具有N端Ile114的完全活性催化结构域。MT1-MMP的催化结构域启动了明胶酶原A以及与金属蛋白酶组织抑制剂-2（TIMP-2）复合的明胶酶原A的激活。作为一种典型的可溶性金属蛋白酶，它能够切割生理底物以及合成底物。我们的动力学数据表明TIMP-2是该重组酶的有效抑制剂。

相似文献

1
The recombinant catalytic domain of membrane-type matrix metalloproteinase-1 (MT1-MMP) induces activation of progelatinase A and progelatinase A complexed with TIMP-2.膜型基质金属蛋白酶-1（MT1-MMP）的重组催化结构域可诱导前明胶酶A以及与组织金属蛋白酶抑制剂-2（TIMP-2）复合的前明胶酶A的激活。
FEBS Lett. 1996 Nov 18;397(2-3):277-82. doi: 10.1016/s0014-5793(96)01206-9.
2
The soluble catalytic domain of membrane type 1 matrix metalloproteinase cleaves the propeptide of progelatinase A and initiates autoproteolytic activation. Regulation by TIMP-2 and TIMP-3.膜型1基质金属蛋白酶的可溶性催化结构域可切割前明胶酶A的前肽并启动自身蛋白水解激活。受金属蛋白酶组织抑制因子-2（TIMP-2）和金属蛋白酶组织抑制因子-3（TIMP-3）调控。
J Biol Chem. 1996 Jul 19;271(29):17119-23. doi: 10.1074/jbc.271.29.17119.
3
Membrane-type-2 matrix metalloproteinase can initiate the processing of progelatinase A and is regulated by the tissue inhibitors of metalloproteinases.膜型-2基质金属蛋白酶可启动前明胶酶A的加工过程，并受金属蛋白酶组织抑制剂的调节。
Eur J Biochem. 1997 Mar 1;244(2):653-7. doi: 10.1111/j.1432-1033.1997.t01-1-00653.x.
4
Activation of progelatinase A and progelatinase A/TIMP-2 complex by membrane type 2-matrix metalloproteinase.2型膜型基质金属蛋白酶对前明胶酶A及前明胶酶A/TIMP-2复合物的激活作用
Biol Chem. 1997 Feb;378(2):71-6. doi: 10.1515/bchm.1997.378.2.71.
5
Tissue inhibitor of metalloproteinases-4 inhibits but does not support the activation of gelatinase A via efficient inhibition of membrane type 1-matrix metalloproteinase.金属蛋白酶组织抑制剂-4通过有效抑制膜型1-基质金属蛋白酶来抑制而非支持明胶酶A的激活。
Cancer Res. 2001 May 1;61(9):3610-8.
6
Sequence motifs of tissue inhibitor of metalloproteinases 2 (TIMP-2) determining progelatinase A (proMMP-2) binding and activation by membrane-type metalloproteinase 1 (MT1-MMP).金属蛋白酶组织抑制剂2（TIMP-2）的序列基序决定了前明胶酶A（proMMP-2）与膜型金属蛋白酶1（MT1-MMP）的结合及激活。
Biochem J. 2003 Jun 15;372(Pt 3):799-809. doi: 10.1042/BJ20021573.
7
Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2.弗林蛋白酶对重组膜型1基质金属蛋白酶（MT1-MMP）的激活及其与金属蛋白酶组织抑制剂（TIMP）-2的相互作用。
FEBS Lett. 1996 Sep 9;393(1):101-4. doi: 10.1016/0014-5793(96)00861-7.
8
Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2.金属蛋白酶组织抑制剂-4（TIMP-4）与人明胶酶A的COOH末端血红素结合蛋白样结构域具有特异性、高亲和力的结合。TIMP-4以与TIMP-2相似的方式结合前明胶酶A和COOH末端结构域。
J Biol Chem. 1997 Jun 13;272(24):15496-500. doi: 10.1074/jbc.272.24.15496.
9
Analysis of tissue inhibitor of metalloproteinases-2 effect on pro-matrix metalloproteinase-2 activation by membrane-type 1 matrix metalloproteinase using baculovirus/insect-cell expression system.利用杆状病毒/昆虫细胞表达系统分析金属蛋白酶组织抑制剂-2对膜型1基质金属蛋白酶激活前基质金属蛋白酶-2的影响。
Biochem J. 2000 Feb 1;345 Pt 3(Pt 3):511-9.
10
Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor.膜型1-基质金属蛋白酶与金属蛋白酶组织抑制剂-2（可溶性前胶原酶A受体）形成的复合物的晶体结构。
EMBO J. 1998 Sep 1;17(17):5238-48. doi: 10.1093/emboj/17.17.5238.

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