| TITLE: | Evidence that the fibrinogen binding domain of Apo(a) is outside the lysine binding site of kringle IV-10: a study involving naturally occurring lysine binding defective lipoprotein(a) phenotypes. | ||||||
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| AUTHOR: | Klezovitch O; Edelstein C; Scanu AM | ||||||
| AUTHOR AFFILIATION: | Department of Medicine, University of Chicago, Illinois 60637, USA. oklezovi@medicine.bsd.uchicago.edu | ||||||
| SOURCE: | J Clin Invest 1996 Jul 1;98(1):185-91 | ||||||
| NLM CIT. ID: | 96294733 | ||||||
| ABSTRACT: | It is now established that the lysine binding site (LBS) of apo(a) kringle IV-10, and particularly Trp72, plays a dominant role in the binding of lipoprotein(a) [Lp(a)] to lysine. To determine the role of the LBS in the binding of Lp(a) to fibrinogen, we examined the binding to plasmin-modified (PM) fibrinogen of human and rhesus monkey Lp(a) species classified as either Lys' or Lys- based on their capacity to bind lysine Sepharose and to have Trp or Arg, respectively, in position 72 of the LBS of kringle IV-10. We also examined the free apo(a)s obtained by subjecting their corresponding parent Lp(a)s to a mild reductive procedure developed in our laboratory. Our results show that both Lyst and Lys- Lp(a)s and their derived apo(a)s, bound to PM-fibrinogen with similar affinities (Kds: 33-100 nM), whereas the B(max) values were threefold higher for apo(a)s. Both the lysine analog epsilon-aminocaproic acid and L-proline inhibited the binding of Lp(a) and apo(a) to PM fibrinogen. We conclude that the LBS of kringle IV-10 is not involved in this process and that apo(a) binds to PM-fibrinogen via a lysine-proline-sensitive domain located outside the LBS and largely masked by the interaction of apo(a) with apoB100. The significant difference in the PM fibrinogen binding capacity also suggests that apo(a) may have a comparatively higher athero-thrombogenic potential than parent Lp(a). | ||||||
| MAIN MESH SUBJECTS: |
Apolipoproteins/*METABOLISM *Kringles Lipoprotein(a)/GENETICS/*METABOLISM | ||||||
| ADDITIONAL MESH SUBJECTS: |
Adult Aged Animal Binding Sites Binding, Competitive Dose-Response Relationship, Drug Female Fibrin Fibrinogen Degradation Products/METABOLISM Human Macaca mulatta Male Middle Age Plasminogen/METABOLISM Protein Binding/DRUG EFFECTS Sepharose/ANALOGS & DERIVATIVES/METABOLISM Support, U.S. Gov't, P.H.S. 6-Aminocaproic Acid/PHARMACOLOGY | ||||||
| PUBLICATION TYPES: | JOURNAL ARTICLE | ||||||
| LANGUAGE: | Eng | ||||||
| REGISTRY NUMBERS: |
0 (apolipoprotein Lp(a+)) 0 (fibrinogen fragment Y) 0 (lysine-sepharose) 0 (Apolipoproteins) 0 (Fibrin Fibrinogen Degradation Products) 0 (Lipoprotein(a)) 60-32-2 (6-Aminocaproic Acid) 9001-91-6 (Plasminogen) 9012-36-6 (Sepharose) | ||||||