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Structure and function comparison of Micropechis ikaheka snake venom phospholipase A 2 isoenzymes
Author(s) -
Lok SheeMei,
Gao Rong,
Rouault Morgane,
Lambeau Gerard,
Gopalakrishnakone Ponnampalam,
Swaminathan Kunchithapadam
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04547.x
Subject(s) - isozyme , snake venom , phospholipase , biochemistry , venom , phospholipase c , structural similarity , receptor , chemistry , biology , stereochemistry , biophysics , enzyme
Comparison of the crystal structures of three Micropechis ikaheka phospholipase A 2 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.