Comparison of ligand-binding sites of modeled apo[a] kringle-like sequences in human lipoprotein[a].
Human lipoprotein[a] contains at least two high-molecular-weight, disulfide-linked apolipoproteins, apo[a] and apo B-100. Apo[a] is a highly glycosylated, hydrophilic apoprotein that somewhat resembles plasminogen by containing an extended kringle domain and a carboxyl-terminal serine protease domain. The apo[a] kringle domain is composed of 11 distinct kringle types. Ten of these display high sequence homology to plasminogen kringle 4 (PGK4). The crystallographic coordinates for PGK4 were used to generate three-dimensional molecular models of the apo[a] kringle types, and the lysine-binding region of PGK4 was used to compare the different potential receptor-ligand and ligand-binding sites contained in each different PGK4-like kringle of apo[a]. A receptor-ligand site can be proposed for each kringle type. Potential serine protease cleavage sites, containing arginine-threonine and threonine-arginine, are located on the surface of the kringles. The ligand-binding site of one apo[a] kringle model is almost identical to that of PGK4 and may be a lysine-binding site of apo[a]. Four other apo[a] kringle models appear to have structurally similar lysine-binding sites, but with differences that may influence ligand-polypeptide specificity. Five apo[a] kringle models have ligand-binding sites that probably do not bind lysine; one of these is the highly repeated kringle in the known apo[a] polymorph.
Department of Medicine, Baylor College of Medicine, Houston, Tex.
J
J
Guevara
A Y
AY
Jan
R
R
Knapp
A
A
Tulinsky
J D
JD
Morrisett
D000595:Amino Acid Sequence; D001054:Apolipoproteins A / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites; D003461:Crystallography / Q000379:methods; D006801:Humans; D008024:Ligands; D017270:Lipoprotein(a) / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics*; D010958:Plasminogen / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D001054:Apolipoproteins A; D008024:Ligands; D017270:Lipoprotein(a); D010446:Peptide Fragments; D010958:Plasminogen