title: Structural and phylogenetic basis for the classification of group III phospholipase A2.
abstract: Secretory phospholipase A2 (PLA2) catalyses the hydrolysis of the sn-2 position of glycerophospholipids to liberate arachidonic acid, a precursor of eicosanoids, that are known mediators of inflammation. The group III PLA2 enzymes are present in a wide array of organisms across many species with completely different functions. A detailed understanding of the structure and evolutionary proximity amongst the enzymes was carried out for a meaningful classification of this group. Fifty protein sequences from different species of the group were considered for a detailed sequence, structural and phylogenetic studies. In addition to the conservation of calcium binding motif and the catalytic histidine, the sequences exhibit specific 'amino acid signatures'. Structural analysis reveals that these enzymes have a conserved globular structure with species specific variations seen at the active site, calcium binding loop, hydrophobic channel, the C-terminal domain and the quaternary conformational state. Character and distance based phylogenetic analysis of these sequences are in accordance with the structural features. The outcomes of the structural and phylogenetic analysis lays a convincing platform for the classification the group III PLA2s into (1A) venomous insects; (IB) non-venomous insects; (II) mammals; (IIIA) gila monsters; (IIIB) reptiles, amphibians, fishes, sea anemones and liver fluke, and (IV) scorpions. This classification also helps to understand structure-function relationship, enzyme-substrate specificity and designing of potent inhibitors against the drug target isoforms.
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, Ansari nagar, New Delhi, 110029, India. g.hariprasad@rediffmail.com
authors.forename: Gururao
authors.initials: G
authors.lastname: Hariprasad
authors.forename: Alagiri
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Reema
authors.initials: R
authors.lastname: Singh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020134:Catalytic Domain; D004220:Disulfides; D054520:Group III Phospholipases A2 / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D004220:Disulfides; D054520:Group III Phospholipases A2; D002118:Calcium