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| | <StructureSection load='6jk6' size='340' side='right'caption='[[6jk6]], [[Resolution|resolution]] 1.57Å' scene=''> | | <StructureSection load='6jk6' size='340' side='right'caption='[[6jk6]], [[Resolution|resolution]] 1.57Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6jk6]] 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=6JK6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JK6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6jk6]] 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=6JK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JK6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BV0:6-azanyl-11-methyl-2-oxidanylidene-7-[[(2R)-oxolan-2-yl]methyl]-N-(pyridin-3-ylmethyl)-1,9-diaza-7-azoniatricyclo[8.4.0.0^{3,8}]tetradeca-3(8),4,6,9,11,13-hexaene-5-carboxamide'>BV0</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.571Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BV0:6-azanyl-11-methyl-2-oxidanylidene-7-[[(2R)-oxolan-2-yl]methyl]-N-(pyridin-3-ylmethyl)-1,9-diaza-7-azoniatricyclo[8.4.0.0^{3,8}]tetradeca-3(8),4,6,9,11,13-hexaene-5-carboxamide'>BV0</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6jk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jk6 OCA], [https://pdbe.org/6jk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jk6 RCSB], [https://www.ebi.ac.uk/pdbsum/6jk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jk6 ProSAT]</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=6jk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jk6 OCA], [http://pdbe.org/6jk6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jk6 RCSB], [http://www.ebi.ac.uk/pdbsum/6jk6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jk6 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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| | </div> | | </div> |
| | <div class="pdbe-citations 6jk6" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6jk6" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Chitinase 3D structures|Chitinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chitinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jiang, X]] | + | [[Category: Jiang X]] |
| - | [[Category: Yang, Q]] | + | [[Category: Yang Q]] |
| - | [[Category: Chitnase]]
| + | |
| - | [[Category: Chitotriosidase]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| 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
Chitinases not only play vital roles in the human innate immune system but are also essential for the development of pathogenic fungi and pests. Chitinase inhibitors are efficient tools to investigate the elusive role of human chitinases and to control pathogens and pests. Via hierarchical virtual screening, we have discovered a series of chitinase inhibitors with a novel scaffold that have high inhibitory activities and selectivities against human and insect chitinases. The most potent human chitotriosidase inhibitor, compound 40, exhibited a Ki of 49 nM, and the most potent inhibitor of the insect pest chitinase OfChi-h, compound 53, exhibited a Ki of 9 nM. The binding of these two most potent inhibitors was confirmed by X-ray crystallography. In a murine model of bleomycin-induced pulmonary fibrosis, compound 40 was found to suppress the chitotriosidase activity by 60%, leading to a significant increase in inflammatory cells and suggesting that chitotriosidase played a protective role.
A Series of Compounds Bearing a Dipyrido-Pyrimidine Scaffold Acting as Novel Human and Insect Pest Chitinase Inhibitors.,Jiang X, Kumar A, Motomura Y, Liu T, Zhou Y, Moro K, Zhang KYJ, Yang Q J Med Chem. 2020 Feb 13;63(3):987-1001. doi: 10.1021/acs.jmedchem.9b01154. Epub, 2020 Feb 3. PMID:31928006[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
- ↑ Jiang X, Kumar A, Motomura Y, Liu T, Zhou Y, Moro K, Zhang KYJ, Yang Q. A Series of Compounds Bearing a Dipyrido-Pyrimidine Scaffold Acting as Novel Human and Insect Pest Chitinase Inhibitors. J Med Chem. 2020 Feb 13;63(3):987-1001. doi: 10.1021/acs.jmedchem.9b01154. Epub, 2020 Feb 3. PMID:31928006 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01154
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