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ISSN 1672-9145                                                Acta Biochim Biophys Sin 2005, 37(5): 283–292                                                   CN 31-1940/Q

Structural Features and Molecular Evolution of Bowman-Birk Protease Inhibitors and Their Potential Application

Rui-Feng QI1,2, Zhan-Wu SONG1, and Cheng-Wu CHI2,3*

 

1College of Life Science, Northwest Normal University, Lanzhou 730070, China;

2Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China;

3Institute of Protein Research, Tongji University, Shanghai 200092, China

 

Abstract        The Bowman-Birk inhibitors (BBIs) are well-studied serine protease inhibitors that are abundant in dicotyledonous and monocotyledonous plants. BBIs from dicots usually have a molecular weight of 8k and are double-headed with two reactive sites, whereas those from monocots can be divided into two classes, one approximately 8 kDa in size with one reactive site (another reactive site was lost) and the other approximately­ 16 kDa in size with two reactive sites. The reactive site is located at unique exposed surfaces formed by a disulfide-linked b-sheet loop that is highly conserved, rigid and mostly composed of nine residues. The structural features and molecular evolution of inhibitors are described, focusing on the conserved­ disulfide bridges. The sunflower trypsin inhibitor-1 (SFTI-1), with 14 amino acid residues, is a recently discovered bicyclic inhibitor, and is the most small and potent naturally occurring Bowman-Birk inhibitor. Recently, BBIs have become a hot topic because of their potential applications. BBIs are now used for defense against pathogens and insects in transgenic plants, which has advantages over using toxic and polluting insecticides. BBIs could also be applied in the prevention of cancer, Dengue fever, and inflammatory­ and allergic disorders, because of their inhibitory activity with respect to the serine proteases that play a pivotal role in the development­ and pathogenesis of these diseases. The canonical nine-residue loop of BBIs/STFI-1 provides an ideal template­ for drug design of specific inhibitors to target their respective­ proteases.

 

Key words        Bowman-Birk protease inhibitor; sunflower trypsin inhibitor-1 (SFTI-1); molecular evolution; drug design

 

 

 

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Received: February 28, 2005        Accepted: March 11, 2005

*Corresponding author: Tel, 86-21-54921165; Fax, 86-21-54921011; E-mail, [email protected]