View source for 2ybt


==Crystal structure of human acidic chitinase in complex with bisdionin C==
<StructureSection load='2ybt' size='340' side='right'caption='[[2ybt]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ybt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YBT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.22&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DW0:1,1-PROPANE-1,3-DIYLBIS(3,7-DIMETHYL-3,7-DIHYDRO-1H-PURINE-2,6-DIONE)'>DW0</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ybt OCA], [https://pdbe.org/2ybt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ybt RCSB], [https://www.ebi.ac.uk/pdbsum/2ybt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ybt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CHIA_HUMAN CHIA_HUMAN] Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to IL-13 and inflammation in response to IL-13. Stimulates chemokine production by pulmonary epithelial cells. Protects lung epithelial cells against apoptosis and promotes phosphorylation of AKT1. Its function in the inflammatory response and in protecting cells against apoptosis is inhibited by allosamidin, suggesting that the function of this protein depends on carbohydrate binding.<ref>PMID:11085997</ref> <ref>PMID:18824549</ref> <ref>PMID:19342690</ref> <ref>PMID:19435888</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Acidic mammalian chitinase (AMCase) is produced in the lung during allergic inflammation and asthma, and inhibition of enzymatic activity has been considered as a therapeutic strategy. However, most chitinase inhibitors are nonselective, additionally inhibiting chitotriosidase activity. Here, we describe bisdionin F, a competitive AMCase inhibitor with 20-fold selectivity for AMCase over chitotriosidase, designed by utilizing the AMCase crystal structure and dicaffeine scaffold. In a murine model of allergic inflammation, bisdionin F-treatment attenuated chitinase activity and alleviated the primary features of allergic inflammation including eosinophilia. However, selective AMCase inhibition by bisdionin F also caused dramatic and unexpected neutrophilia in the lungs. This class of inhibitor will be a powerful tool to dissect the functions of mammalian chitinases in disease and represents a synthetically accessible scaffold to optimize inhibitory properties in terms of airway inflammation.

Analyzing Airway Inflammation with Chemical Biology: Dissection of Acidic Mammalian Chitinase Function with a Selective Drug-like Inhibitor.,Sutherland TE, Andersen OA, Betou M, Eggleston IM, Maizels RM, van Aalten D, Allen JE Chem Biol. 2011 May 27;18(5):569-79. PMID:21609838<ref>PMID:21609838</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2ybt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Chitinase 3D structures|Chitinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Allen JE]]
[[Category: Andersen OA]]
[[Category: Betou M]]
[[Category: Eggleston IM]]
[[Category: Maizels RM]]
[[Category: Sutherland TE]]
[[Category: Van Aalten D]]