9mnb: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Beta1-tryptase monomer bound to inhibitory Fabs E82.AS and E104.v2== | |||
<StructureSection load='9mnb' size='340' side='right'caption='[[9mnb]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9mnb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9MNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MNB FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3Å</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=9mnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mnb OCA], [https://pdbe.org/9mnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mnb RCSB], [https://www.ebi.ac.uk/pdbsum/9mnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mnb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRYB1_HUMAN TRYB1_HUMAN] Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human beta-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of inflammatory responses in asthma, allergy and other diseases. Here we report an anti-beta-tryptase antibody with a superior mechanism of action compared to others since it not only inhibits tetrameric beta-tryptase, but also completely inhibits monomeric beta-tryptase activity. The antibody binds to an exosite that causes tetramer dissociation as either an IgG or Fab and, in addition, allosterically alters the substrate binding cleft on monomers, thus preventing substrate binding and proteolysis. We solve the cryoEM structure of the complex, generate biochemical data and engineer point mutations to elucidate the allosteric path of inhibition. This ultimately reveals a single Asp to Gly mutation in CDR-L3 that only slightly impacts binding affinity, but completely eliminates inhibitory activity. Finally, we improve antibody inhibitory potency up to 4.7-fold by structure-based design creating new charge-charge interactions. This antibody may have enhanced efficacy and potential to assess the relevance of beta-tryptase, including monomers, in biological and clinical settings. | |||
Complete inhibition of beta-tryptase by tetramer dissociation and active site allostery due to a single antibody residue.,Maun HR, Azumaya CM, Walters BT, Vij R, Morando A, Loyet KM, Koerber JT, Rohou A, Lazarus RA Nat Commun. 2026 Apr 9;17(1):3393. doi: 10.1038/s41467-026-70491-3. PMID:41957026<ref>PMID:41957026</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9mnb" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Azumaya CM]] | |||
[[Category: Maun HR]] | |||
[[Category: Rohou AL]] | |||
Latest revision as of 06:24, 22 April 2026
Beta1-tryptase monomer bound to inhibitory Fabs E82.AS and E104.v2
| ||||||||||||
