5Y1B

Crystal Structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with a berberine derivative (SYSU-00679)

Summary for 5Y1B

• Entry DOI: 10.2210/pdb5y1b/pdb
• Descriptor: Beta-hexosaminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose, 9-O-3'-quinolinium propylberberine, ... (4 entities in total)
• Functional Keywords: ostrinia furnacalis, beta-n-acetyl-d-hexosaminidase inhibitor, berberine derivative, hydrolase
• Biological source: Ostrinia furnacalis (Asian corn borer)
• Total number of polymer chains: 1
• Total formula weight: 67315.78

Authors

Duan, Y.W.,Liu, T.,Zhou, Y.,Tang, J.Y.,Li, M.,Yang, Q. (deposition date: 2017-07-20, release date: 2018-01-24, Last modification date: 2024-10-23)

Primary citation

Duan, Y.,Liu, T.,Zhou, Y.,Dou, T.,Yang, Q.
Glycoside hydrolase family 18 and 20 enzymes are novel targets of the traditional medicine berberine.
J. Biol. Chem., 293:15429-15438, 2018

PubMed Abstract: Berberine 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 β--acetyl-d-hexosaminidase (GH20 Hex) and GH18 chitinase from both humans and the insect pest Berberine and its analog SYSU-1 inhibit insect GH20 Hex from (Hex1), with values of 12 and 8.5 μm, respectively. Co-crystallization of berberine and its analog SYSU-1 in complex with Hex1 revealed that the positively charged conjugate plane of berberine forms π-π stacking interactions with Trp, which are vital to its inhibitory activity. Moreover, the 1,3-dioxole group of berberine binds an unexplored pocket formed by Trp, Trp, and Val, which also contributes to its inhibitory activity. Berberine was also found to be an inhibitor of human GH20 Hex (HexB), human GH18 chitinase (Cht and acidic mammalian chitinase), and insect GH18 chitinase (ChtI). Besides GH18 and GH20 enzymes, berberine was shown to weakly inhibit human GH84 GlcNAcase (OGA) and GH63 α-glucosidase I (GluI). By analyzing the published crystal structures, berberine was revealed to bind with its targets in an identical mechanism, namely via π-π 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.

PubMed: 30135205
DOI: 10.1074/jbc.RA118.004351

Experimental method

X-RAY DIFFRACTION (2.207 Å)