REVIEW: Role of A-Chain in Functioning of the Active Site of Human alpha-Thrombin

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M. V. Kolodzeiskaya, L. I. Sokolovskaya^*, and G. L. Volkov

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, ul. Leontovicha 9, 01601 Kiev, Ukraine; fax: 38 (044) 235-5172; E-mail: sokludmila@yandex.ru

^* To whom correspondence should be addressed.

Received April 12, 2007; Revision received September 5, 2007

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This review summarizes current data suggesting that A-chain of the human alpha-thrombin molecule plays a role of allosteric effector in catalytic reactions with various substrates. Special attention is paid to the relationship between A-chain structure and catalytic activity of thrombin. The existence of this relationship is based on studies of natural mutation of A-chain of the alpha-thrombin molecule. Use of molecular and essential dynamics confirmed the role of A-chain in changes of conformation and catalytic properties of this enzyme; these changes involve residues located in the specificity sites and some inserting loops. Current knowledge on structure and properties of thrombin can be used for the development of new antithrombin agents.

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KEY WORDS: thrombin, allosterics, mutagenesis, protein C, modulation, thrombomodulin, molecular dynamics

DOI: 10.1134/S0006297908030012

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