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| | <StructureSection load='4wkh' size='340' side='right'caption='[[4wkh]], [[Resolution|resolution]] 1.05Å' scene=''> | | <StructureSection load='4wkh' size='340' side='right'caption='[[4wkh]], [[Resolution|resolution]] 1.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wkh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WKH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wkh]] 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=4WKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WKH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CBS:DI(N-ACETYL-D-GLUCOSAMINE)'>CBS</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1guv|1guv]]</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=4wkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wkh OCA], [https://pdbe.org/4wkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wkh RCSB], [https://www.ebi.ac.uk/pdbsum/4wkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wkh ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wkh OCA], [http://pdbe.org/4wkh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wkh RCSB], [http://www.ebi.ac.uk/pdbsum/4wkh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wkh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chitinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cachau, R]] | + | [[Category: Cachau R]] |
| - | [[Category: Cousido-Siah, A]] | + | [[Category: Cousido-Siah A]] |
| - | [[Category: Fadel, F]] | + | [[Category: Fadel F]] |
| - | [[Category: Harlos, K]] | + | [[Category: Harlos K]] |
| - | [[Category: Howard, E]] | + | [[Category: Howard E]] |
| - | [[Category: Mitschler, A]] | + | [[Category: Mitschler A]] |
| - | [[Category: Podjarny, A]] | + | [[Category: Podjarny A]] |
| - | [[Category: Ruiz, F X]] | + | [[Category: Ruiz FX]] |
| - | [[Category: Zhao, Y]] | + | [[Category: Zhao Y]] |
| - | [[Category: Catalytic mechanism]]
| + | |
| - | [[Category: Chit1]]
| + | |
| - | [[Category: Gh18 chitinase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolysis]]
| + | |
| - | [[Category: Protonation state]]
| + | |
| Structural highlights
Function
CHIT1_HUMAN Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Boot RG, Renkema GH, Strijland A, van Zonneveld AJ, Aerts JM. Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages. J Biol Chem. 1995 Nov 3;270(44):26252-6. PMID:7592832
- ↑ Renkema GH, Boot RG, Muijsers AO, Donker-Koopman WE, Aerts JM. Purification and characterization of human chitotriosidase, a novel member of the chitinase family of proteins. J Biol Chem. 1995 Feb 3;270(5):2198-202. PMID:7836450
- ↑ Boot RG, Renkema GH, Verhoek M, Strijland A, Bliek J, de Meulemeester TM, Mannens MM, Aerts JM. The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem. 1998 Oct 2;273(40):25680-5. PMID:9748235
- ↑ Fadel F, Zhao Y, Cachau R, Cousido-Siah A, Ruiz FX, Harlos K, Howard E, Mitschler A, Podjarny A. New insights into the enzymatic mechanism of human chitotriosidase (CHIT1) catalytic domain by atomic resolution X-ray diffraction and hybrid QM/MM. Acta Crystallogr D Biol Crystallogr. 2015 Jul 1;71(Pt 7):1455-70. doi:, 10.1107/S139900471500783X. Epub 2015 Jun 30. PMID:26143917 doi:http://dx.doi.org/10.1107/S139900471500783X
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