7C34

Crystal structure of Serratia marcescens Chitinase B complexed with Berberine

Summary for 7C34

• Entry DOI: 10.2210/pdb7c34/pdb
• Descriptor: Chitinase, BERBERINE (3 entities in total)
• Functional Keywords: serratia marcescens, chitinase b, berberine, hydrolase
• Biological source: Serratia marcescens
• Total number of polymer chains: 2
• Total formula weight: 111130.05

Authors

Chen, L.,Chen, J.,Yang, Q. (deposition date: 2020-05-11, release date: 2020-05-27, Last modification date: 2024-10-09)

Primary citation

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, 35:1937-1943, 2020

PubMed Abstract: 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 values ranging between 20 and 70 μM. In this report, we present for the first time the berberine-complexed crystal structure of ChiB, a model GH18 chitinase from the bacterium . 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 showed 80-fold-elevated inhibitory activity against ChiB and the human chitinase hAMCase with 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.

PubMed: 33167737
DOI: 10.1080/14756366.2020.1837123

Experimental method

X-RAY DIFFRACTION (1.938 Å)