View source for 4wka


==Crystal structure of human chitotriosidase-1 catalytic domain at 0.95 A resolution==
<StructureSection load='4wka' size='340' side='right'caption='[[4wka]], [[Resolution|resolution]] 0.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wka]] is a 1 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=4WKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WKA 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]] 0.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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=4wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wka OCA], [https://pdbe.org/4wka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wka RCSB], [https://www.ebi.ac.uk/pdbsum/4wka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wka ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CHIT1_HUMAN CHIT1_HUMAN] Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.<ref>PMID:7592832</ref> <ref>PMID:7836450</ref> <ref>PMID:9748235</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Chitotriosidase (CHIT1) is a human chitinase belonging to the highly conserved glycosyl hydrolase family 18 (GH18). GH18 enzymes hydrolyze chitin, an N-acetylglucosamine polymer synthesized by lower organisms for structural purposes. Recently, CHIT1 has attracted attention owing to its upregulation in immune-system disorders and as a marker of Gaucher disease. The 39 kDa catalytic domain shows a conserved cluster of three acidic residues, Glu140, Asp138 and Asp136, involved in the hydrolysis reaction. Under an excess concentration of substrate, CHIT1 and other homologues perform an additional activity, transglycosylation. To understand the catalytic mechanism of GH18 chitinases and the dual enzymatic activity, the structure and mechanism of CHIT1 were analyzed in detail. The resolution of the crystals of the catalytic domain was improved from 1.65 A (PDB entry 1waw) to 0.95-1.10 A for the apo and pseudo-apo forms and the complex with chitobiose, allowing the determination of the protonation states within the active site. This information was extended by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. The results suggest a new mechanism involving changes in the conformation and protonation state of the catalytic triad, as well as a new role for Tyr27, providing new insights into the hydrolysis and transglycosylation activities.

New insights into the enzymatic mechanism of human chitotriosidase (CHIT1) catalytic domain by atomic resolution X-ray diffraction and hybrid QM/MM.,Fadel F, Zhao Y, Cachau R, Cousido-Siah A, Ruiz FX, Harlos K, Howard E, Mitschler A, Podjarny A Acta Crystallogr D Biol Crystallogr. 2015 Jul 1;71(Pt 7):1455-70. doi:, 10.1107/S139900471500783X. Epub 2015 Jun 30. PMID:26143917<ref>PMID:26143917</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wka" style="background-color:#fffaf0;"></div>

==See Also==
*[[Chitinase 3D structures|Chitinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cachau R]]
[[Category: Cousido-Siah A]]
[[Category: Fadel F]]
[[Category: Harlos K]]
[[Category: Howard E]]
[[Category: Mitschler A]]
[[Category: Podjarny A]]
[[Category: Ruiz FX]]
[[Category: Zhao Y]]