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PDBsum entry 1s6e
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Membrane protein
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PDB id
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1s6e
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References listed in PDB file
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Key reference
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Title
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Crystal structure of a calcium-Induced dimer of two isoforms of cobra phospholipase a2 at 1.6 a resolution.
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Authors
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T.Jabeen,
S.Sharma,
N.Singh,
R.K.Singh,
P.Kaur,
M.Perbandt,
C.H.Betzel,
A.Srinivasan,
T.P.Singh.
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Ref.
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Proteins, 2005,
59,
856-863.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 3.
Figure 3. PLA[2] activity with varying calcium ion
concentration. The molar ratio of enzyme and calcium is shown on
the X-axis while the percent activity is indicated on Y-axis.
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Figure 5.
Figure 5. A: Calcium binding loop of molecule B with the final
|2F[o] - Fc| electron density for the calcium ion drawn at 4
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The calcium coordinations with loop residues, Asp 49, phosphate
ion and the water molecule are also indicated. B: Superposition
of the calcium binding loops of molecules A (green) and B
(yellow). The calcium free loop of molecule A adopts a narrow
conformation. C: Calcium binding loop of molecule A. The
arginine 31 from molecule B is also shown. The intraloop
hydrogen bond between Cys27 O and Gly33 N is indicated by green
dotted line. D: The final |2F[o] - Fc| electron density for the
calcium ion drawn at 4 at
the interface of the two molecules. Calcium coordinated
intermolecular interactions are indicated by dotted lines. The
coordination is sevenfold with trigonal bipyramidal geometry.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2005,
59,
856-863)
copyright 2005.
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