Structure and function comparison of Micropechis ikaheka snake venom phospholipase A2 isoenzymes.
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.
Lok
Shee-Mei
SM
Institute of Molecular and Cell Biology, Singapore.
Gao
Rong
R
Rouault
Morgane
M
Lambeau
Gerard
G
Gopalakrishnakone
Ponnampalam
P
Swaminathan
Kunchithapadam
K
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
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