Crystal structures of BnSP-7 and BnSP-6, two Lys49-phospholipases A(2): quaternary structure and inhibition mechanism insights

Biochem Biophys Res Commun. 2003 Nov 21;311(3):713-20. doi: 10.1016/j.bbrc.2003.10.047.

Abstract

Phospholipases A(2) are components of Bothrops venoms responsible for disruption of cell membrane integrity via hydrolysis of its phospholipids. A class of PLA(2)-like proteins has been described which despite PLA(2) activity on artificial substrate, due to a D49K mutation, is still highly myonecrotic. This work reports the X-ray structure determination of two Lys49-PLA(2)s from Bothrops neuwiedi pauloensis (BnSP-7 and BnSP-6) and, for the first time, the comparison of eight dimeric Lys49-PLA(2)s. This comparison reveals that there are not just two ("open" and "closed") but at least six different conformations. The binding of fatty acid observed in three recent Lys49-PLA(2) structures seems to be independent of their quaternary conformation. Cys29 polarization by Lys122 is not significant for BnSP-7 and BnSP-6 or other structures not bound by fatty acids. These structures may be in an "active" state when nothing is bound to them and the Lys122/Cys29 interactions are weak or absent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bothrops
  • Catalysis
  • Crotalid Venoms / chemistry*
  • Crystallography, X-Ray
  • DNA, Complementary / metabolism
  • Electrons
  • Fatty Acids / chemistry
  • Group II Phospholipases A2
  • Lysine / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Phospholipases A / chemistry*
  • Phospholipases A2
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Quaternary
  • Reptilian Proteins
  • Sequence Homology, Amino Acid

Substances

  • Crotalid Venoms
  • DNA, Complementary
  • Fatty Acids
  • Reptilian Proteins
  • BnSP-6
  • Phospholipases A
  • Group II Phospholipases A2
  • Lys49-phospholipase A2, Bothrops neuwiedi pauloensis
  • Phospholipases A2
  • Lysine