title: Structure and function comparison of Micropechis ikaheka snake venom phospholipase A2 isoenzymes.
abstract: Comparison of the crystal structures of three Micropechis ikaheka phospholipase A2 isoenzymes (MiPLA2, MiPLA3 and MiPLA4, which exhibit different levels of pharmacological effects) shows that their C-terminus (residues 110-124) is the most variable. M-Type receptor binding affinity of the isoenzymes has also been investigated and MiPLA4 binds to the rabbit M-type receptor with high affinity. Examination of surface charges of the isoenzymes reveals a trend of increase in positive charges with potency. The isoenzymes are shown to oligomerize in a concentration-dependent manner in a semi-denaturing gel. The C-termini of the medium (MiPLA4) and highly potent (MiPLA2) isoenzyme molecules cluster together, forming a highly exposed area. A BLAST search using the sequence of the most potent MiPLA2 results in high similarity to Staphylococcus aureus clotting factor A and cadherin 11. This might explain the myotoxicity, anticoagulant and hemoglobinuria effects of MiPLA2s.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore.
authors.forename: Shee-Mei
authors.initials: SM
authors.lastname: Lok
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.forename: Morgane
authors.initials: M
authors.lastname: Rouault
authors.forename: Gerard
authors.initials: G
authors.lastname: Lambeau
authors.forename: Ponnampalam
authors.initials: P
authors.lastname: Gopalakrishnakone
authors.forename: Kunchithapadam
authors.initials: K
authors.lastname: Swaminathan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003402:Creatine Kinase / Q000097:blood; D018360:Crystallography, X-Ray; D004546:Elapid Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017815:Elapidae; D010450:Endopeptidases / Q000378:metabolism; D054500:Group IB Phospholipases A2; D006456:Hemoglobinuria / Q000378:metabolism; D007527:Isoenzymes; D051379:Mice; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity*; D010741:Phospholipases A / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D054467:Phospholipases A2; D011487:Protein Conformation; D011516:Prothrombin / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D054507:Receptors, Phospholipase A2; D030162:Reptilian Proteins; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000378:metabolism
chemical_list: D004546:Elapid Venoms; D007527:Isoenzymes; D009498:Neurotoxins; C516357:Pla2r1 protein, mouse; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D030162:Reptilian Proteins; D011516:Prothrombin; D003402:Creatine Kinase; D010741:Phospholipases A; D054500:Group IB Phospholipases A2; D054467:Phospholipases A2; D010450:Endopeptidases; C019914:clotting enzyme