Chemical modifications of phospholipases A2 from snake venoms: effects on catalytic and pharmacological properties.
Phospholipases A2 (PLA2s) constitute major components of snake venoms and have been extensively investigated not only because they are very abundant in these venoms but mainly because they display a wide range of biological effects, including neurotoxic, myotoxic, cytotoxic, edema-inducing, artificial membrane disrupting, anti-coagulant, platelet aggregation inhibiting, hypotensive, bactericidal, anti-HIV, anti-tumoral, anti-malarial and anti-parasitic. Due to this functional diversity, these structurally similar proteins aroused the interest of many researchers as molecular models for study of structure-function relationships. One of the main experimental strategies used for the study of myotoxic PLA2s is the traditional chemical modification of specific amino acid residues (His, Met, Lys, Tyr, Trp and others) and examination of the consequent effects upon the enzymatic, toxic and pharmacological activities. This line of research has provided useful insights into the structural determinants of the action of these enzymes and, together with additional strategies, supports the concept of the presence of 'pharmacological sites' distinct from the catalytic site in snake venom myotoxic PLA2s.
Soares
Andreimar M
AM
Departamento de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirão Presto, SP, Brazil. andreimar@unarep.br
Giglio
José R
JR
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D006639:Histidine / Q000378:metabolism; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000378:metabolism* / Q000494:pharmacology*; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D012910:Snake Venoms / Q000201:enzymology*; D012911:Snakes; D013329:Structure-Activity Relationship
D000596:Amino Acids; D012910:Snake Venoms; D006639:Histidine; D010741:Phospholipases A