6o1f: Difference between revisions
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<StructureSection load='6o1f' size='340' side='right'caption='[[6o1f]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='6o1f' size='340' side='right'caption='[[6o1f]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6o1f]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O1F OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6o1f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Glycine_max Glycine max] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O1F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O1F FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=6o1f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o1f OCA], [https://pdbe.org/6o1f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o1f RCSB], [https://www.ebi.ac.uk/pdbsum/6o1f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o1f ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6o1f" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6o1f" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Trypsin inhibitor 3D structures|Trypsin inhibitor 3D structures]] | |||
*[[Tryptase|Tryptase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Glycine max]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ultsch MH]] | |||
[[Category: Ultsch | [[Category: Yi T]] | ||
[[Category: Yi | |||
Latest revision as of 10:03, 11 October 2023
Complex between soybean trypsin inhibitor beta1-tryptase and a humanized fabComplex between soybean trypsin inhibitor beta1-tryptase and a humanized fab
Structural highlights
FunctionTRYB1_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). Publication Abstract from PubMedSevere asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active beta-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human beta-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 A crystal structure of a beta-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma. An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma.,Maun HR, Jackman JK, Choy DF, Loyet KM, Staton TL, Jia G, Dressen A, Hackney JA, Bremer M, Walters BT, Vij R, Chen X, Trivedi NN, Morando A, Lipari MT, Franke Y, Wu X, Zhang J, Liu J, Wu P, Chang D, Orozco LD, Christensen E, Wong M, Corpuz R, Hang JQ, Lutman J, Sukumaran S, Wu Y, Ubhayakar S, Liang X, Schwartz LB, Babina M, Woodruff PG, Fahy JV, Ahuja R, Caughey GH, Kusi A, Dennis MS, Eigenbrot C, Kirchhofer D, Austin CD, Wu LC, Koerber JT, Lee WP, Yaspan BL, Alatsis KR, Arron JR, Lazarus RA, Yi T Cell. 2019 Oct 3;179(2):417-431.e19. doi: 10.1016/j.cell.2019.09.009. PMID:31585081[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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