5y0v: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal Structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with berberine== | ==Crystal Structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with berberine== | ||
<StructureSection load='5y0v' size='340' side='right' caption='[[5y0v]], [[Resolution|resolution]] 2.42Å' scene=''> | <StructureSection load='5y0v' size='340' side='right'caption='[[5y0v]], [[Resolution|resolution]] 2.42Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5y0v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Asian_corn_borer Asian corn borer]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y0V OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5y0v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Asian_corn_borer Asian corn borer]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y0V OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5Y0V FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BER:BERBERINE'>BER</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | </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>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5y0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y0v OCA], [http://pdbe.org/5y0v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y0v RCSB], [http://www.ebi.ac.uk/pdbsum/5y0v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y0v ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 20: | Line 20: | ||
==See Also== | ==See Also== | ||
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]] | *[[Beta-Hexosaminidase|Beta-Hexosaminidase]] | ||
*[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 26: | Line 27: | ||
[[Category: Asian corn borer]] | [[Category: Asian corn borer]] | ||
[[Category: Beta-N-acetylhexosaminidase]] | [[Category: Beta-N-acetylhexosaminidase]] | ||
[[Category: Large Structures]] | |||
[[Category: Duan, Y W]] | [[Category: Duan, Y W]] | ||
[[Category: Li, M]] | [[Category: Li, M]] | ||
Revision as of 10:02, 14 October 2020
Crystal Structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with berberineCrystal Structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with berberine
Structural highlights
Publication Abstract from PubMedBerberine is a traditional medicine that has multiple medicinal and agricultural applications. However, little is known about whether berberine can be a bioactive molecule toward carbohydrate-active enzymes, which play numerous vital roles in the life process. In this study, berberine and its analogs were discovered to be competitive inhibitors of glycoside hydrolase family 20 beta-N-acetyl-d-hexosaminidase (GH20 Hex) and GH18 chitinase from both humans and the insect pest Ostrinia furnacalis Berberine and its analog SYSU-1 inhibit insect GH20 Hex from O. furnacalis (OfHex1), with Ki values of 12 and 8.5 mum, respectively. Co-crystallization of berberine and its analog SYSU-1 in complex with OfHex1 revealed that the positively charged conjugate plane of berberine forms pi-pi stacking interactions with Trp(490), which are vital to its inhibitory activity. Moreover, the 1,3-dioxole group of berberine binds an unexplored pocket formed by Trp(322), Trp(483), and Val(484), which also contributes to its inhibitory activity. Berberine was also found to be an inhibitor of human GH20 Hex (HsHexB), human GH18 chitinase (HsCht and acidic mammalian chitinase), and insect GH18 chitinase (OfChtI). Besides GH18 and GH20 enzymes, berberine was shown to weakly inhibit human GH84 O-GlcNAcase (HsOGA) and Saccharomyces cerevisiae GH63 alpha-glucosidase I (ScGluI). By analyzing the published crystal structures, berberine was revealed to bind with its targets in an identical mechanism, namely via pi-pi stacking and electrostatic interactions with the aromatic and acidic residues in the binding pockets. This paper reports new molecular targets of berberine and may provide a berberine-based scaffold for developing multitarget drugs. Glycoside hydrolase family 18 and 20 enzymes are novel targets of the traditional medicine berberine.,Duan Y, Liu T, Zhou Y, Dou T, Yang Q J Biol Chem. 2018 Oct 5;293(40):15429-15438. doi: 10.1074/jbc.RA118.004351. Epub , 2018 Aug 22. PMID:30135205[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||