3H6S

Structure of clitocypin - cathepsin V complex

3H6S の概要

• エントリーDOI: 10.2210/pdb3h6s/pdb
• 関連するPDBエントリー: 3H6Q 3H6R
• 分子名称: Cathepsin L2, Clitocypin analog, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: cathepsin, clitocypin, kunitz inhibitor, cysteine protease, disulfide bond, glycoprotein, hydrolase, lysosome, protease, thiol protease, zymogen, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Lysosome : O60911
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 164583.34

構造登録者

Renko, M.,Sabotic, J.,Brzin, J.,Turk, D. (登録日: 2009-04-23, 公開日: 2009-10-20, 最終更新日: 2021-10-13)

主引用文献

Renko, M.,Sabotic, J.,Mihelic, M.,Brzin, J.,Kos, J.,Turk, D.
Versatile loops in mycocypins inhibit three protease families.
J.Biol.Chem., 285:308-316, 2010

PubMed Abstract: Mycocypins, clitocypins and macrocypins, are cysteine protease inhibitors isolated from the mushrooms Clitocybe nebularis and Macrolepiota procera. Lack of sequence homology to other families of protease inhibitors suggested that mycocypins inhibit their target cysteine protease by a unique mechanism and that a novel fold may be found. The crystal structures of the complex of clitocypin with the papain-like cysteine protease cathepsin V and of macrocypin and clitocypin alone have revealed yet another motif of binding to papain like-cysteine proteases, which in a yet unrevealed way occludes the catalytic residue. The binding is associated with a peptide-bond flip of glycine that occurs before or concurrently with the inhibitor docking. Mycocypins possess a beta-trefoil fold, the hallmark of Kunitz-type inhibitors. It is a tree-like structure with two loops in the root region, a stem comprising a six-stranded beta-barrel, and two layers of loops (6 + 3) in the crown region. The two loops that bind to cysteine cathepsins belong to the lower layer of the crown loops, whereas a single loop from the crown region can inhibit trypsin or asparaginyl endopeptidase, as demonstrated by site-directed mutagenesis. These loops present a versatile surface with the potential to bind to additional classes of proteases. When appropriately engineered, they could provide the basis for possible exploitation in crop protection.

PubMed: 19846555
DOI: 10.1074/jbc.M109.043331

実験手法

X-RAY DIFFRACTION (2.22 Å)