Identification of a novel and potent inhibitor of phospholipase A2 in a medicinal plant: Crystal structure at 1.93 Å and Surface Plasmon Resonance analysis of phospholipase A2 complexed with berberine

被引:29
作者
Chandra, D. Naveen [1 ,2 ]
Prasanth, G. K. [1 ,2 ]
Singh, Nagendra [3 ]
Kumar, Sanjit [3 ]
Jithesh, O. [3 ]
Sadasivan, C. [1 ,2 ]
Sharma, Sujatha [3 ]
Singh, Tej P. [3 ]
Haridas, M. [1 ,2 ]
机构
[1] Kannur Univ, Dept Biotechnol & Microbiol, Palayad 670661, Kerala, India
[2] Kannur Univ, Inter Univ Ctr Biosci, Palayad 670661, Kerala, India
[3] All India Inst Med Sci, Dept Biophys, New Delhi 110029, India
来源
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS | 2011年 / 1814卷 / 05期
关键词
Phospholipase A(2) inhibition; Berberine; X-ray crystallography; Surface Plasmon Resonance; PROTEIN;
D O I
10.1016/j.bbapap.2011.03.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Crystal of Russell Viper venom phospholipase A(2) complexed with an isoquinoline alkaloid, berberine from a herbaceous plant Cardiospermum halicacabum, was prepared and its structure was solved by X-ray crystallography. The crystal diffracted up to 1.93 angstrom and the structure solution clearly located the position of berberine in the active site of the enzyme. Two hydrogen bonds, one direct and the other water mediated, were formed between berberine and the enzyme. Gly 30 and His 48 made these two hydrogen bonds. Additionally, the hydrophobic surface of berberine made a number of hydrophobic contacts with side chains of neighboring amino acids. Surface Plasmon Resonance studies revealed strong binding affinity between berberine and phospholipase A(2). Enzyme inhibition studies proved that berberine is a competitive inhibitor of phospholipase A(2). It was inferred that the isoquinoline alkaloid, berberine, is a potent natural inhibitor of phospholipase A(2). (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:657 / 663
页数:7
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