3h6s | pdb_00003h6s
Structure of clitocypin - cathepsin V complex
Structural highlights
Function[CATL2_HUMAN] Cysteine protease. May have an important role in corneal physiology.[1] [2] [CLIT5_CLINE] Binds and inhibits cysteine proteinases. Inhibits most strongly papain and cathepsin L, more weakly bromelain and cathepsin B while it is completely ineffective against cathepsin H.[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMycocypins, 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. Versatile loops in mycocypins inhibit three protease families.,Renko M, Sabotic J, Mihelic M, Brzin J, Kos J, Turk D J Biol Chem. 2010 Jan 1;285(1):308-16. Epub 2009 Oct 21. PMID:19846555[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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