Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea.
Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea.
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DOI：
10.3390/ijms23094916
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发表时间：
2022-04-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
我们从蘑菇Coprinopsis cinerea中引入了一个新的具有β-三叶折叠的真菌蛋白酶抑制剂家族，命名为cocapins，它可以抑制半胱氨酸和天冬氨酸蛋白酶。两个cocapin编码基因在真菌组织中有差异表达。一个在营养菌丝体中高度转录，另一个在成熟子实体的茎柱中高度转录。cocapins是一种小蛋白质（15 kDa），具有酸性等电点，形成二聚体。cocaprin 1的三维结构与真菌β-三叶凝集素相似。cocapins对植物C1家族半胱氨酸蛋白酶的抑制作用在微摩尔范围内，但不抑制C13家族蛋白酶豆科蛋白酶，这与mycocypins不同。在低微摩尔范围内，椰角素还能抑制天冬氨酸蛋白酶胃蛋白酶。诱变表明，β2-β3环参与抑制半胱氨酸蛋白酶，并且天冬氨酸蛋白酶和半胱氨酸蛋白酶的抑制活性位点位于蛋白质上的不同位置。它们的生物学功能被认为是调节内源性蛋白水解活性或防御真菌拮抗剂。cocapins是第一个从真菌中发现的具有β-三叶折叠的天冬氨酸蛋白酶抑制剂，并证明了具有β-三叶折叠的真菌蛋白的环功能化的令人难以置信的可塑性。
We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fruiting bodies. Cocaprins are small proteins (15 kDa) with acidic isoelectric points that form dimers. The three-dimensional structure of cocaprin 1 showed similarity to fungal β-trefoil lectins. Cocaprins inhibit plant C1 family cysteine proteases with Ki in the micromolar range, but do not inhibit the C13 family protease legumain, which distinguishes them from mycocypins. Cocaprins also inhibit the aspartic protease pepsin with Ki in the low micromolar range. Mutagenesis revealed that the β2-β3 loop is involved in the inhibition of cysteine proteases and that the inhibitory reactive sites for aspartic and cysteine proteases are located at different positions on the protein. Their biological function is thought to be the regulation of endogenous proteolytic activities or in defense against fungal antagonists. Cocaprins are the first characterized aspartic protease inhibitors with β-trefoil fold from fungi, and demonstrate the incredible plasticity of loop functionalization in fungal proteins with β-trefoil fold.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1016/j.bbapap.2014.07.004
发表时间：
2014-10-01
影响因子：
3.2
作者：
Caglic, Petra Avanzo;Renko, Miha;Sabotic, Jerica
通讯作者：
Sabotic, Jerica
影响因子：
4.1
作者：
HENDERSON, PJ
通讯作者：
HENDERSON, PJ
影响因子：
3.2
作者：
Garcia-Mesa, Yoelvis;Jay, Taylor R.;Alvarez-Carbonell, David
通讯作者：
Alvarez-Carbonell, David
DOI：
10.1073/pnas.0801343105
发表时间：
2008-07-29
影响因子：
11.1
作者：
Gosavi, Shachi;Whitford, Paul C.;Onuchic, Jose N.
通讯作者：
Onuchic, Jose N.