The human alpha(2)-plasmin inhibitor: functional characterization of the unique plasmin(ogen)-binding region.

Cellular and Molecular Life Sciences : CMLS
Simon S GerberJ Schaller

Abstract

The human alpha(2)-plasmin inhibitor (A2PI) possesses unique N- and C-terminal extensions that significantly influence its biological activities. The C-terminal segment, A2PIC (Asn(398)-Lys(452)), contains six lysines thought to be involved in the binding to lysine-binding sites in the kringle domains of human plasminogen, of which four (Lys(422), Lys(429), Lys(436), Lys(452)) are completely and two (Lys(406), Lys(415)) are partially conserved. Multiple Lys to Ala mutants of A2PIC were expressed in Escherichia coli and used in intrinsic fluorescence titrations with kringle domains K1, K4, K4 + 5, and K1 + 2 + 3 of human plasminogen. We were able to identify the C-terminal Lys(452) as the main binding partner in recombinant A2PIC (rA2PIC) constructs with isolated kringles. We could show a cooperative, zipper-like enhancement of the interaction between C-terminal Lys(452) and internal Lys(436) of rA2PIC and isolated K1 + 2 + 3, whereas the other internal lysine residues contribute only to a minor extent to the binding process. Sulfated Tyr(445) in the unique C-terminal segment revealed no influence on the binding affinity to kringle domains.

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Citations

May 6, 2011·The Journal of Biological Chemistry·Bernadine G C LuAnita J Horvath
Dec 8, 2010·Cellular and Molecular Life Sciences : CMLS·Johann Schaller, Simon S Gerber
Dec 3, 2015·Blood·Shiraazkhan AbdulShirley Uitte de Willige
Nov 26, 2013·The Biochemical Journal·Simon M CookJason D McArthur
Dec 18, 2009·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Guojun ChenBingqian Xu
Nov 18, 2020·Brain Research Bulletin·Mingyue WangDongdong Qin
Oct 28, 2019·Biochemical and Biophysical Research Communications·Agata Hanna BrykAnetta Undas

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