1s6b

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(New page: 200px<br /><applet load="1s6b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s6b, resolution 1.60&Aring;" /> '''X-ray Crystal Struct...)
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[[Image:1s6b.gif|left|200px]]<br /><applet load="1s6b" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1s6b, resolution 1.60&Aring;" />
caption="1s6b, resolution 1.60&Aring;" />
'''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'''<br />
'''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'''<br />
==Overview==
==Overview==
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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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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==
==About this Structure==
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1S6B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Naja_sagittifera Naja sagittifera] with CA, PO4 and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 1LFJ. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S6B OCA].
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1S6B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Naja_sagittifera Naja sagittifera] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1LFJ. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S6B OCA].
==Reference==
==Reference==
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[[Category: Kaur, P.]]
[[Category: Kaur, P.]]
[[Category: Sharma, S.]]
[[Category: Sharma, S.]]
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[[Category: Singh, R.K.]]
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[[Category: Singh, R K.]]
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[[Category: Singh, T.P.]]
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[[Category: Singh, T P.]]
[[Category: ACY]]
[[Category: ACY]]
[[Category: CA]]
[[Category: CA]]
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[[Category: phospholipase a2]]
[[Category: phospholipase a2]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:08:57 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:58:25 2008''

Revision as of 12:58, 21 February 2008


1s6b, resolution 1.60Å

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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 , and as ligands. This structure supersedes 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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