Regulation of catalytic function by molecular association: structure of phospholipase A(2) from Daboia russelli pulchella (DPLA(2)) at 1.9 angstrom resolution

The crystal structure of phospholipase A(2) from the venom of Daboia russel li pulchella has been refined to an R factor of 0.216 using 17922 reflectio ns to 1.9 Angstrom resolution. The structure contains two crystallographica lly independent molecules in the asymmetric unit. The overall conformations of the two molecules are essentially the same except for three regions, na mely the calcium-binding loop including Trp31, the beta -wing and the C-ter minal residues 119-131. Although these differences have apparently been cau sed by molecular packing, they seem to have functional relevance. Particula rly noteworthy is the conformation of Trp31, which is favourable for substr ate binding in one molecule as it is aligned with one of the side walls of the hydrophobic channel, whereas in the other molecule it is located at the mouth of the channel, thereby blocking the entry of substrates leading to loss of activity. This feature is unique to the present structure and does not occur in the dimers and trimers of other PLA(2)s.