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| | <StructureSection load='6jk9' size='340' side='right'caption='[[6jk9]], [[Resolution|resolution]] 2.31Å' scene=''> | | <StructureSection load='6jk9' size='340' side='right'caption='[[6jk9]], [[Resolution|resolution]] 2.31Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6jk9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus marcescens" (bizio 1823) trevisan in de toni and trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JK9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JK9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6jk9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JK9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BU0:6-azanyl-2-oxidanylidene-N-[(1S)-1-phenylethyl]-7-(phenylmethyl)-1$l^{4},9-diaza-7-azoniatricyclo[8.4.0.0^{3,8}]tetradeca-1(14),3(8),4,6,10,12-hexaene-5-carboxamide'>BU0</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]] 2.312Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">chiB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=615 "Bacillus marcescens" (Bizio 1823) Trevisan in de Toni and Trevisan 1889])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BU0:2-amino-1-benzyl-5-oxo-3-{[(1S)-1-phenylethyl]carbamoyl}-5,11-dihydrodipyrido[1,2-a 2,3-d]pyrimidine-1,6-diium'>BU0</scene></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=6jk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jk9 OCA], [http://pdbe.org/6jk9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jk9 RCSB], [http://www.ebi.ac.uk/pdbsum/6jk9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jk9 ProSAT]</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=6jk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jk9 OCA], [https://pdbe.org/6jk9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jk9 RCSB], [https://www.ebi.ac.uk/pdbsum/6jk9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jk9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CHIB_SERMA CHIB_SERMA] |
| | <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 6jk9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6jk9" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Chitinase 3D structures|Chitinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jiang, X]] | + | [[Category: Serratia marcescens]] |
| - | [[Category: Yang, Q]] | + | [[Category: Jiang X]] |
| - | [[Category: Chitianse]] | + | [[Category: Yang Q]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Serratia marcescen]]
| + | |
| Structural highlights
Function
CHIB_SERMA
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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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