6jkf: Difference between revisions
New page: '''Unreleased structure''' The entry 6jkf is ON HOLD Authors: Yang, Q., Jiang, X. Description: Crystal structure of Serratia marcescens Chitinase B complexed with compound 2-8-s2 [[Cat... |
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==Crystal structure of Serratia marcescens Chitinase B complexed with compound 2-8-s2== | |||
<StructureSection load='6jkf' size='340' side='right'caption='[[6jkf]], [[Resolution|resolution]] 1.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6jkf]] 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=6JKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JKF 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]] 1.99Å</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-[[(2~{R})-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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6jkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jkf OCA], [https://pdbe.org/6jkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jkf RCSB], [https://www.ebi.ac.uk/pdbsum/6jkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jkf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CHIB_SERMA CHIB_SERMA] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:31928006</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6jkf" style="background-color:#fffaf0;"></div> | ||
[[Category: Jiang | |||
==See Also== | |||
*[[Chitinase 3D structures|Chitinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Serratia marcescens]] | |||
[[Category: Jiang X]] | |||
[[Category: Yang Q]] | |||
Latest revision as of 08:21, 21 November 2024
Crystal structure of Serratia marcescens Chitinase B complexed with compound 2-8-s2Crystal structure of Serratia marcescens Chitinase B complexed with compound 2-8-s2
Structural highlights
FunctionPublication Abstract from PubMedChitinases 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 AlsoReferences
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