Journal:Acta Cryst F:S2053230X20000199
From Proteopedia
Structure of MP-4 from Mucuna pruriens at 2.22 Å resolutionAbha Jain, Amit Kumar, Meha Shikhi, Ashish Kumar, Deepak T. Nair and Dinakar M. Salunke [1] Molecular Tour Intro Para: MP-4 is a protein purified from Mucuna pruriens and it belongs to the Kunitz type of protease inhibitor (KPTI) family. However, biochemical experiments showed that MP-4 is a poor inhibitor of proteases such as trypsin. It has been shown that MP-4 provides protection against snake venom through an indirect antibody based mechanism [2]. Previously, MP-4 structure was determined at a lower resolution, and due to lack of availability of the gene sequence, the assignment of residues, especially of the C-terminal region was based primarily on electron density. The present structure is determined at higher resolution and the improved maps enabled better identification of the side chains. Recently, the genome sequence of Mucuna pruriens became available and confirmed the protein sequence derived based on the electron density maps was correct. The present structure reinforces the idea that the polypeptide sequence of proteins purified from source can be determined using electron density maps if the resolution is sufficiently high. Overall Structure: The adapts β-trefoil fold and this fold is known to be the signature of Kunitz type of protease inhibitors. A total of 179 residues of MP-4 form 12 β-strands arranged in β-hairpin like conformation connected by long loops. The tertiary structure is further stabilized by two disulphide bonds with the first one formed between residues and the second one between . Functional Para: As the name suggests Kunitz type of protease inhibitors (KPTI) are responsible for inhibiting activity of certain proteases like trypsin. To inhibit proteases, the reactive site loop is known to occupy the active site groove of the target enzyme. and forms a loop in 6jbp. The residue at the P1 position of the RSL is the principal residue that decides the inhibitory efficiency of protease inhibitor [3][4]. In functional KTPIs, the P1 position (69th residue) is usually occupied by Arg, Lys, Phe, Tyr, Leu or Met but the electron density map clearly shows that . The presence of Ile at P1 position may be responsible for weak inhibitory activity exhibited by MP-4 [5]. PDB reference: MP-4, 6jbp. References
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