tailieunhanh - Báo cáo khoa học: Identification and characterization of plasma kallikrein–kinin system inhibitors from salivary glands of the blood-sucking insect Triatoma infestans

Two plasma kallikrein–kinin system inhibitors in the salivary glands of the kissing bugTriatoma infestans, designated triafestin-1 and triafestin-2, have been identified and characterized. Reconstitution experiments showed that triafestin-1 and triafestin-2 inhibit the activation of the kallikrein–kinin sys-tem by inhibiting the reciprocal activation of factor XII and prekallikrein, and subsequent release of bradykinin. | ỊFEBS Journal Identification and characterization of plasma kallikrein-kinin system inhibitors from salivary glands of the blood-sucking insect Triatoma infestans 1 1-2 - 3ai-i- -2 Haruhiko Isawa Yuki Orito Naruhiro Jingushi Siroh Iwanaga Akihiro Morita Yasuo Chinzei and Masao Yuda2 1 Department of MedicalEntomology National institute of Infectious Diseases Tokyo Japan 2 Department of MedicalZoology Schoolof Medicine Mie University Japan 3 Laboratory of Chemistry and Utilization of AnimalResources Faculty of Agriculture Kobe University Japan Keywords factor XII high molecular weight kininogen kallikrein kinin system salivary gland Triatoma infestans Correspondence H. Isawa Department of Medical Entomology NationalInstitute of Infectious Diseases Toyama 1-23-1 Sinjuku-ku Tokyo 162-8640 Japan Fax 81 3 5285 1147 Tel 81 3 5285 1111 E-mail hisawa@ Received 20 February 2007 revised 18 June 2007 accepted 27 June 2007 doi Two plasma kallikrein-kinin system inhibitors in the salivary glands of the kissing bug Triatoma infestans designated triafestin-1 and triafestin-2 have been identified and characterized. Reconstitution experiments showed that triafestin-1 and triafestin-2 inhibit the activation of the kallikrein-kinin system by inhibiting the reciprocal activation of factor XII and prekallikrein and subsequent release of bradykinin. Binding analyses showed that triafes-tin-1 and triafestin-2 specifically interact with factor XII and high molecular weight kininogen in a Zn2 -dependent manner suggesting that they specifically recognize Zn2 -induced conformational changes in factor XII and high molecular weight kininogen. Triafestin-1 and triafestin-2 also inhibit factor XII and high molecular weight kininogen binding to negatively charged surfaces. Furthermore they interact with both the N-terminus of factor XII and domain D5 of high molecular weight kininogen which are the binding domains for biological activating .