Crystal structures of BnSP-7 and BnSP-6, two Lys49-phospholipases A(2): quaternary structure and inhibition mechanism insights.
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.
Magro
Angelo J
AJ
Departamento de Física e Biofísica, IB, UNESP, Botucatu-SP, Brazil.
Soares
Andreimar M
AM
Giglio
José R
JR
Fontes
Marcos R M
MR
D000595:Amino Acid Sequence; D000818:Animals; D017837:Bothrops; D002384:Catalysis; D003435:Crotalid Venoms / Q000737:chemistry*; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000378:metabolism; D004583:Electrons; D005227:Fatty Acids / Q000737:chemistry; D054501:Group II Phospholipases A2; D008239:Lysine / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000737:chemistry*; D054467:Phospholipases A2; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D030162:Reptilian Proteins; D017386:Sequence Homology, Amino Acid
D003435:Crotalid Venoms; D018076:DNA, Complementary; D005227:Fatty Acids; D030162:Reptilian Proteins; C479860:BnSP-6; D010741:Phospholipases A; D054501:Group II Phospholipases A2; C410627:Lys49-phospholipase A2, Bothrops neuwiedi pauloensis; D054467:Phospholipases A2; D008239:Lysine