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Lipoprotein(a) (Lp(a)), a risk factor for coronary artery
disease, is a LDL-like particle with apolipoprotein(a) (apo(a))
covalently linked to apolipoprotein B (apoB), the main protein
component of LDL. Apo(a) is highly homologous to plasminogen and its
gene probably arose by duplication of the plasminogen gene. It has many
repeats of kringle-4-like domain, classified as type 1 through type 10
(T1-T10). T9 is responsible for the covalent linkage between
apo(a) and LDL. However, we found that T9 has no affinity for LDL.
Therefore, an initial noncovalent interaction between apo(a) and LDL is
necessary to bring T9 and LDL together. T6 and possibly T7 of apo(a)
were identified as the kringles which mediate this initial interaction.
With these findings, a two-step model for Lp(a) formation is proposed.
This model should be useful in the design of Lp(a) formation
inhibitors. These inhibitors are potential anti-hyperlipoprotein(a)
drugs.
Volume 270,
Number 26,
Issue of June 30, pp. 15471-15474, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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