7e50: Difference between revisions
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7e50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e50 OCA], [https://pdbe.org/7e50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e50 RCSB], [https://www.ebi.ac.uk/pdbsum/7e50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e50 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7e50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e50 OCA], [https://pdbe.org/7e50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e50 RCSB], [https://www.ebi.ac.uk/pdbsum/7e50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e50 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== | <div style="background-color:#fffaf0;"> | ||
== 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<ref>PMID:34800067</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7e50" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Plasminogen 3D structures|Plasminogen 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 12:23, 9 October 2024
Crystal structure of human microplasmin in complex with kazal-type inhibitor AaTICrystal structure of human microplasmin in complex with kazal-type inhibitor AaTI
Structural highlights
Publication Abstract from PubMedKazal-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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