1s6b

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spinqualitylabelsall models 1s6b, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

X-ray Crystal Structure of a Complex Formed Between Two Homologous Isoforms of Phospholipase A2 from Naja naja sagittifera: Principle of Molecular Association and Inactivation

Overview

The calcium-induced formation of a complex between two isoforms of cobra, venom phospholipase A2 reveals a novel interplay between the monomer-dimer, and activity-inactivity transitions. The monodispersed isoforms lack, activity in the absence of calcium ions while both molecules gain activity, in the presence of calcium ions. At concentrations higher than 10 mg/ml, in the presence of calcium ions, they dimerize and lose activity again., The present study reports the crystal structure of a calcium-induced dimer, between two isoforms of cobra phospholipase A2. In the complex, one, molecule contains a calcium ion in the calcium binding loop while the, second molecule does not possess an intramolecular calcium ion. However, there are two calcium ions per dimer in the structure. The second calcium, ion is present at an intermolecular site and that is presumably, responsible for the dimerization. The calcium binding loops of the two, molecules adopt strikingly different conformations. The so-called calcium, binding loop in the calcium-containing molecule adopts a normal, conformation as generally observed in other calcium containing, phospholipase A(2) enzymes while the conformation of the corresponding, loop in the calcium free monomer deviates considerably with the formation, of a unique intraloop Gly33 (N)-Cys27 (O) = 2.74 A backbone hydrogen bond., The interactions of Arg31 (B) with Asp49 (A) and absence of calcium ion, are responsible for the loss of catalytic activity in molecule A while, interactions of Arg2 (B) with Tyr52 (B) inactivate molecule B.

About this Structure

1S6B is a Protein complex structure of sequences from Naja sagittifera with CA, PO4 and ACY as ligands. This structure superseeds the now removed PDB entry 1LFJ. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.

Reference

Crystal structure of a calcium-induced dimer of two isoforms of cobra phospholipase A2 at 1.6 A resolution., Jabeen T, Sharma S, Singh N, Singh RK, Kaur P, Perbandt M, Betzel Ch, Srinivasan A, Singh TP, Proteins. 2005 Jun 1;59(4):856-63. PMID:15828003

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