Crystallographic and biochemical studies of the (inactive) Lys-49 phospholipase A2 from the venom of Agkistridon piscivorus piscivorus.
Chemical, genetic, and structural studies have defined a critical role for Asp-49 in the calcium-mediated activation of extracellular phospholipases A2 (PLA2). In 1984, a new class of PLA2 was isolated in which this invariant aspartate was replaced with a lysine (Maragnore, J.M., Merutka, G., Cho, W., Welches, W., Kezdy, F.J., and Heinrikson, R.L. (1984) J. Biol. Chem. 259, 13839-13843; Maragnore, J.M., and Heinrikson, R.L. (1986) J. Biol. Chem. 261, 4797-4804). The enzymatic activity of Lys-49 PLA2s has been questioned based on biochemical, mutational, and structural studies (van den Bergh, C.J., Slotboom, A.J., Verheij, H.M., and de Haas, G.H. (1988) Eur. J. Biochem. 176, 353-357). In this paper, we describe the structures of two crystal forms of the Lys-49 PLA2 isolated from the venom of Agkistridon piscivorus piscivorus. The refined models, along with complementary biochemical analysis, clarify the structural basis for the enzymatic inactivity of Lys-49 proteins.
Scott
D L
DL
Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637.
Achari
A
A
Vidal
J C
JC
Sigler
P B
PB
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D003461:Crystallography; D008239:Lysine; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000648:ultrastructure*; D054467:Phospholipases A2; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012910:Snake Venoms / Q000201:enzymology*; D013329:Structure-Activity Relationship
D012910:Snake Venoms; D010741:Phospholipases A; D054467:Phospholipases A2; D008239:Lysine