Subunit structure and inhibition specificity of alpha-type phospholipase A2 inhibitor from Protobothrops flavoviridis.
The alpha-type phospholipase A2 inhibitor (PLIalpha) in the plasma of the Habu snake, Protobothrop flavoviridis, was shown to be a trimer of two homologous subunits, PLIalpha-A and PLIalpha-B, each of which contains one C-type lectin-like domain (CTLD). Since one molecule of trimeric PLIalpha binds stoichiometrically to one molecule of P. flavoviridis acidic phospholipase A2 (PLA2), the trimeric structure is critical for its inhibitory activity. Hydrophobic chromatography separated the purified P. flavoviridis PLIalpha into four different trimeric subspecies, A3-PLIalpha, A2B-PLIalpha, AB2-PLIalpha, and B3-PLIalpha, with different combinations of the two subunits. The trimeric PLIalpha could be reconstituted from the purified subunits, and the four different trimeric subspecies were formed through random association of the two subunits. The inhibitory activity of the PLIalpha-A homotrimer (A3-PLIalpha) was more specific than that of the PLIalpha-B homotrimer (B3-PLIalpha). This difference in inhibitory properties between the two homotrimers was probably caused by the amino acid differences at residues 10-37.
Shimada
Akiko
A
Laboratory of Biochemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Ohkura
Naoki
N
Hayashi
Kyozo
K
Samejima
Yuji
Y
Omori-Satoh
Tamotsu
T
Inoue
Seiji
S
Ikeda
Kiyoshi
K
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D054467:Phospholipases A2 / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits; D013997:Time Factors; D017819:Viperidae / Q000097:blood* / Q000378:metabolism
D001798:Blood Proteins; C400481:PLIalpha; D021122:Protein Subunits; D054467:Phospholipases A2