1oqs
Crystal Structure of RV4/RV7 ComplexCrystal Structure of RV4/RV7 Complex
Structural highlights
Function[PA2A7_DABSI] Heterodimer: RV-4/RV-7 targets the presynaptic sites of the neuromuscular junction.[1] Monomer: snake venom phospholipase A2 (PLA2) RV-7 that has low enzymatic activity and is not toxic. It inhibits the enzymatic activity of RV-4 in vitro but potentiates its lethal potency and neurotoxicity. It may facilitate the specific binding of RV-4 to its presynaptic binding sites, probably by acting as a chaperon, minimizing distraction and destruction of RV-4 en route to the site of action by reducing non-specific binding to muscle and other organs. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.[2] [PA2B4_DABSI] Heterodimer RV-4/RV-7: acts as a presynaptic neurotoxin. Monomer: snake venom phospholipase A2 (PLA2) that acts as a presynaptic neurotoxin. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe presynaptic viperotoxin F is the major lethal component of the venom of Vipera russelli formosensis (Taiwan viper). It is a heterodimer of two highly homologous (65% identity) but oppositely charged subunits: a basic and neurotoxic PLA(2) (RV-4) and an acidic non-toxic component with a very low enzymatic activity (RV-7). The crystal structure of the complex has been determined by molecular replacement and refined to 1.9 A resolution and an R factor of 22.3% with four RV-4/RV-7 complexes in the asymmetric unit, which do not exhibit any local point-group symmetry. The complex formation decreases the accessible surface area of the two subunits by approximately 1425 A(2). Both PLA(2)s are predicted to have very low, if any, anticoagulant activity. The structure of viperotoxin F is compared with that of the heterodimeric neurotoxin vipoxin from the venom of another viper, V. ammodytes meridionalis. The structural basis for the differences between the pharmacological activities of the two toxins is discussed. The neutralization of the negative charge of the major ligand for Ca(2+), Asp49, by intersubunit salt bridges is probably a common mechanism of self-stabilization of heterodimeric Viperinae snake-venom neurotoxins in the absence of bound calcium. Structure of the heterodimeric neurotoxic complex viperotoxin F (RV-4/RV-7) from the venom of Vipera russelli formosensis at 1.9 A resolution.,Perbandt M, Tsai IH, Fuchs A, Banumathi S, Rajashankar KR, Georgieva D, Kalkura N, Singh TP, Genov N, Betzel C Acta Crystallogr D Biol Crystallogr. 2003 Oct;59(Pt 10):1679-87. Epub 2003, Sep 19. PMID:14501106[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||