1S8H

Crystal structure of Lys49-Phospholipase A2 from Agkistrodon contortrix laticinctus, first fatty acid free form

Summary for 1S8H

• Entry DOI: 10.2210/pdb1s8h/pdb
• Related: 1s8g 1s8i
• Descriptor: Phospholipase A2 homolog, SULFATE ION (3 entities in total)
• Functional Keywords: lys49-phospholipase a2, snake venom, myotoxicity, fatty acid free form, hydrolase, toxin
• Biological source: Agkistrodon contortrix laticinctus (broad-banded copperhead)
• Cellular location: Secreted: P49121
• Total number of polymer chains: 1
• Total formula weight: 14145.45

Authors

Ambrosio, A.L.B.,de Souza, D.H.F.,Nonato, M.C.,Selistre de Araujo, H.S.,Ownby, C.L.,Garratt, R.C. (deposition date: 2004-02-02, release date: 2004-02-10, Last modification date: 2011-07-13)

Primary citation

Ambrosio, A.L.B.,Nonato, M.C.,Selistre de Araujo, H.S.,Arni, R.,Ward, R.J.,Ownby, C.L.,de Souza, D.H.F.,Garratt, R.C.
A Molecular Mechanism for Lys49-Phospholipase A2 Activity Based on Ligand-induced Conformational Change.
J.Biol.Chem., 280:7326-7335, 2005

PubMed Abstract: Agkistrodon contortrix laticinctus myotoxin is a Lys(49)-phospholipase A(2) (EC 3.1.1.4) isolated from the venom of the serpent A. contortrix laticinctus (broad-banded copperhead). We present here three monomeric crystal structures of the myotoxin, obtained under different crystallization conditions. The three forms present notable structural differences and reveal that the presence of a ligand in the active site (naturally presumed to be a fatty acid) induces the exposure of a hydrophobic surface (the hydrophobic knuckle) toward the C terminus. The knuckle in A. contortrix laticinctus myotoxin involves the side chains of Phe(121) and Phe(124) and is a consequence of the formation of a canonical structure for the main chain within the region of residues 118-125. Comparison with other Lys(49)-phospholipase A(2) myotoxins shows that although the knuckle is a generic structural motif common to all members of the family, it is not readily recognizable by simple sequence analyses. An activation mechanism is proposed that relates fatty acid retention at the active site to conformational changes within the C-terminal region, a part of the molecule that has long been associated with Ca(2+)-independent membrane damaging activity and myotoxicity. This provides, for the first time, a direct structural connection between the phospholipase "active site" and the C-terminal "myotoxic site," justifying the otherwise enigmatic conservation of the residues of the former in supposedly catalytically inactive molecules.

PubMed: 15596433
DOI: 10.1074/jbc.M410588200

Experimental method

X-RAY DIFFRACTION (1.8 Å)