Biomaterial Database

Structure-function relationships of phospholipases. The anticoagulant region of phospholipases A2. 1987

R M Kini, and H J Evans

Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.

In an effort to identify the anticoagulant region of venom phospholipases A2, we have systematically compared the amino acid sequences of strong, weak and non-anticoagulant phospholipases. The comparison disclosed several significant substitutions in the region between residues 54 and 77 (homology numbers). This proposed anticoagulant region is positively charged in strong, but negatively charged in weak and non-anticoagulant phospholipases. The microenvironment of a tryptophan residue falls within the proposed region, accounting for the differential characteristics of intrinsic fluorescence changes observed at 335 nm after the binding of phospholipid vesicles to strong and weak anticoagulants. Four lysine residues are located in specific positions in the "anticoagulant" region of strong anticoagulants, and should form a cationic surface, based on analogy with the available crystallographic structures. The chemical modification of lysine, arginine, tyrosine, and tryptophan residues and carboxylate groups, performed by other investigators, not only provides added support for the predicted site, but also confirms the essentiality of the positive charges in the site. This region may participate in the formation of a specific preferential hydrolytic complex leading to the strong anticoagulant effect. The anticoagulant region is distinct and separate from the predicted neurotoxic and myotoxic sites, and is located on the opposite surface of the phospholipase molecule.

UI	MeSH Term	Description	Entries
D008239	Lysine	An essential amino acid. It is often added to animal feed.	Enisyl,L-Lysine,Lysine Acetate,Lysine Hydrochloride,Acetate, Lysine,L Lysine
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010740	Phospholipases	A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-.	Lecithinases,Lecithinase,Phospholipase
D010741	Phospholipases A	Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D003439	Crotoxin	A specific complex of toxic proteins from the venom of Crotalus durissus terrificus (South American rattlesnake). It can be separated into a phospholipase A and crotapotin fragment; the latter consists of three different amino acid chains, potentiates the enzyme, and is specifically neurotoxic.	Crotapotin,Crotoxin A,Crotoxin B
D004546	Elapid Venoms	Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.	Cobra Venoms,Elapidae Venom,Elapidae Venoms,Naja Venoms,Cobra Venom,Elapid Venom,Hydrophid Venom,Hydrophid Venoms,King Cobra Venom,Naja Venom,Ophiophagus hannah Venom,Sea Snake Venom,Sea Snake Venoms,Venom, Cobra,Venom, Elapid,Venom, Elapidae,Venom, Hydrophid,Venom, King Cobra,Venom, Naja,Venom, Ophiophagus hannah,Venom, Sea Snake,Venoms, Cobra,Venoms, Elapid,Venoms, Elapidae,Venoms, Hydrophid,Venoms, Naja,Venoms, Sea Snake
D005453	Fluorescence	The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis.
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000925	Anticoagulants	Agents that prevent BLOOD CLOTTING.	Anticoagulant Agent,Anticoagulant Drug,Anticoagulant,Anticoagulant Agents,Anticoagulant Drugs,Anticoagulation Agents,Indirect Thrombin Inhibitors,Agent, Anticoagulant,Agents, Anticoagulant,Agents, Anticoagulation,Drug, Anticoagulant,Drugs, Anticoagulant,Inhibitors, Indirect Thrombin,Thrombin Inhibitors, Indirect
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships