7e50

Crystal structure of human microplasmin in complex with kazal-type inhibitor AaTI

spinqualitylabelsall models 7e50, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7e50 is a 2 chain structure with sequence from Aedes aegypti and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: GOL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Kazal-type protease inhibitor specificity is believed to be determined by sequence of the reactive-site loop that make most, if not all, contacts with the serine protease. Here, we determined the complex crystal structure of Aedes aegypti trypsin inhibitor (AaTI) with mu-plasmin, and compared its reactivities with other Kazal-type inhibitors, infestin-1 and infestin-4. We show that the shortened 99-loop of plasmin creates an S2 pocket, which is filled by phenylalanine at the P2 position of the reactive-site loop of infestin-4. In contrast, AaTI and infestin-1 retain a proline at P2, rendering the S2 pocket unfilled, which leads to lower plasmin inhibitions. Furthermore, the protein scaffold of AaTI is unstable, due to an elongated Cys-V to Cys-VI region leading to a less compact hydrophobic core. Chimeric study shows that the stability of the scaffold can be modified by swapping of this Cys-V to Cys-VI region between AaTI and infestin-4. The scaffold instability causes steric clashing of the bulky P2 residue, leading to significantly reduced inhibition of plasmin by AaTI or infestin-4 chimera. Our findings suggest that surface loops of protease and scaffold stability of Kazal-type inhibitor are both necessary for specific protease inhibition, in addition to reactive site loop sequence. PDB ID code: 7E50. Crystal structure of Aedes aegypti trypsin inhibitor in complex with mu-plasmin reveals role for scaffold stability in Kazal-type serine protease inhibitor.,Walvekar VA, Ramesh K, Jobichen C, Kannan M, Sivaraman J, Kini RM, Mok YK Protein Sci. 2022 Feb;31(2):470-484. doi: 10.1002/pro.4245. Epub 2021 Nov 29. PMID:34800067 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Plasminogen 3D structures

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