6BVH
Trypsin complexed with a modified sunflower trypsin inhibitor, SFTI-TCTR(N12,N14)
Summary for 6BVH
| Entry DOI | 10.2210/pdb6bvh/pdb |
| Descriptor | Cationic trypsin, Trypsin inhibitor 1, CALCIUM ION, ... (6 entities in total) |
| Functional Keywords | protease inhibitor complex, sunflower trypsin inhibitor, sfti, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Bos taurus (Bovine) More |
| Total number of polymer chains | 2 |
| Total formula weight | 25494.63 |
| Authors | Riley, B.T.,Chen, X. (deposition date: 2017-12-13, release date: 2018-12-19, Last modification date: 2024-11-20) |
| Primary citation | Chen, X.,Riley, B.T.,de Veer, S.J.,Hoke, D.E.,Van Haeften, J.,Leahy, D.,Swedberg, J.E.,Brattsand, M.,Hartfield, P.J.,Buckle, A.M.,Harris, J.M. Potent, multi-target serine protease inhibition achieved by a simplified beta-sheet motif. PLoS ONE, 14:e0210842-e0210842, 2019 Cited by PubMed Abstract: Engagement of an extended β-sheet is a common substrate/inhibitor interaction at the active site of serine proteases and is an important feature of Laskowski mechanism inhibitors that present a substrate-like loop to a target protease. This loop is cleaved but subsequently relegated forming a stable inhibitor/protease complex. Laskowski inhibitors are ubiquitous in nature and are used extensively in serine protease inhibitor design. However, most studies concentrate on introducing new sidechain interactions rather than the direct contributions of the substrate-like β-sheet to enzyme inhibition. Here we report the crystal structure of an simplified β-sheet inhibitory motif within the Sunflower Trypsin Inhibitor (SFTI) in complex with trypsin. We show that the intramolecular hydrogen bond network of this SFTI variant (SFTI-TCTR) engages the inhibitor sidechains that would normally interact with a target protease, giving mainchain interactions a more prominent role in complex formation. Despite having reduced sidechain interactions, this SFTI variant is remarkably potent and inhibits a diverse range of serine proteases. Crystal structural analysis and molecular modelling of SFTI-TCTR complexes again indicates an interface dominated by β-sheet interactions, highlighting the importance of this motif and the adaptability of SFTI as a scaffold for inhibitor design. PubMed: 30668585DOI: 10.1371/journal.pone.0210842 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.927 Å) |
Structure validation
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