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| | <StructureSection load='7c34' size='340' side='right'caption='[[7c34]], [[Resolution|resolution]] 1.94Å' scene=''> | | <StructureSection load='7c34' size='340' side='right'caption='[[7c34]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7c34]] 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=7C34 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C34 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7c34]] 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=7C34 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C34 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BER:BERBERINE'>BER</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]] 1.938Å</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=BER:BERBERINE'>BER</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c34 OCA], [http://pdbe.org/7c34 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c34 RCSB], [http://www.ebi.ac.uk/pdbsum/7c34 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c34 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=7c34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c34 OCA], [https://pdbe.org/7c34 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c34 RCSB], [https://www.ebi.ac.uk/pdbsum/7c34 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c34 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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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, J]] | + | [[Category: Serratia marcescens]] |
| - | [[Category: Chen, L]] | + | [[Category: Chen J]] |
| - | [[Category: Yang, Q]] | + | [[Category: Chen L]] |
| - | [[Category: Berberine]] | + | [[Category: Yang Q]] |
| - | [[Category: Chitinase b]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Serratia marcescen]]
| + | |
| Structural highlights
Function
CHIB_SERMA
Publication Abstract from PubMed
Glycoside hydrolase family 18 (GH18) chitinases play an important role in various organisms ranging from bacteria to mammals. Chitinase inhibitors have potential applications as pesticides, fungicides, and anti-asthmatics. Berberine, a plant-derived isoquinoline alkaloid, was previously reported to inhibit against various GH18 chitinases with only moderate K i values ranging between 20 and 70 muM. In this report, we present for the first time the berberine-complexed crystal structure of SmChiB, a model GH18 chitinase from the bacterium Serratia marcescens. Based on the berberine-binding mode, a hydrophobic cavity-based optimisation strategy was developed to increase their inhibitory activity. A series of berberine derivatives were designed and synthesised, and their inhibitory activities against GH18 chitinases were evaluated. The compound 4c showed 80-fold-elevated inhibitory activity against SmChiB and the human chitinase hAMCase with K i values at the sub-micromolar level. The mechanism of improved inhibitory activities was proposed. This work provides a new strategy for developing novel chitinase inhibitors.
Crystal structure-guided design of berberine-based novel chitinase inhibitors.,Chen L, Zhu L, Chen J, Chen W, Qian X, Yang Q J Enzyme Inhib Med Chem. 2020 Dec;35(1):1937-1943. doi:, 10.1080/14756366.2020.1837123. PMID:33167737[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen L, Zhu L, Chen J, Chen W, Qian X, Yang Q. Crystal structure-guided design of berberine-based novel chitinase inhibitors. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1937-1943. doi:, 10.1080/14756366.2020.1837123. PMID:33167737 doi:http://dx.doi.org/10.1080/14756366.2020.1837123
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