An examination of structural interactions presumed to be of importance in the stabilization of phospholipase A2 dimers based upon comparative protein sequence analysis of a monomeric and dimeric enzyme from the venom of Agkistrodon p. piscivorus.
Phospholipases A2 may exist in solution both as monomers and dimers, but enzymes that form strong dimers (KD approximately 10(-9) M) have been found, thus far, only in venoms of the snake family Crotilidae. The complete amino acid sequences of a basic monomeric and an acidic dimeric phospholipase A2 from Agkistrodon piscivorus piscivorus (American cottonmouth water moccasin) venom have been determined by protein sequencing methods as part of a search for aspects of structure contributing to formation of stable dimers. Both the monomeric and dimeric phospholipases A2 are highly homologous to the dimeric phospholipases A2 from Crotalus atrox and Crotalus adamanteus venoms, and both have the seven residue carboxy-terminal extension characteristic of the crotalid and viperid enzymes. Thus, it is clear that the extension is not a prerequisite for dimerization. Studies to date have revealed two characteristic features of phospholipases A2 that exist in solution as strong dimers. One is the presence in the dimers of a Pro-Pro sequence at position 112 and 113 which just precedes the seven residue carboxy-terminal extension (residues 116-122). The other is a low isoelectric point; only the acidic phospholipases A2 have been observed, thus far, to form stable dimers. These, alone or together, may be necessary, though not sufficient conditions for phospholipase A2 dimer formation. Ideas regarding subunit interactions based upon crystallographic data are evaluated relative to the new sequence information on the monomeric and dimeric phospholipases A2 from A.p. piscivorus venom.
Welches
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Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195.
Reardon
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Heinrikson
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D000595:Amino Acid Sequence; D003435:Crotalid Venoms / Q000737:chemistry*; D004795:Enzyme Stability; D008969:Molecular Sequence Data; D010455:Peptides; D010741:Phospholipases A / Q000737:chemistry*; D054467:Phospholipases A2; D011108:Polymers; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D009626:Terminology as Topic
C031442:Agkistrodon venoms; D003435:Crotalid Venoms; D010455:Peptides; D011108:Polymers; D010741:Phospholipases A; D054467:Phospholipases A2