1bci
From Proteopedia
(New page: 200px<br /> <applet load="1bci" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bci" /> '''C2 DOMAIN OF CYTOSOLIC PHOSPHOLIPASE A2, NM...) |
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'''C2 DOMAIN OF CYTOSOLIC PHOSPHOLIPASE A2, NMR, MINIMIZED AVERAGE STRUCTURE'''<br /> | '''C2 DOMAIN OF CYTOSOLIC PHOSPHOLIPASE A2, NMR, MINIMIZED AVERAGE STRUCTURE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The amino-terminal, 138 amino acid C2 domain of cytosolic phospholipase A2 | + | The amino-terminal, 138 amino acid C2 domain of cytosolic phospholipase A2 (cPLA2-C2) mediates an initial step in the production of lipid mediators of inflammation: the Ca2+-dependent translocation of the enzyme to intracellular membranes with subsequent liberation of arachidonic acid. The high resolution solution structure of this Ca2+-dependent, lipid-binding domain (CaLB) has been determined using heteronuclear three-dimensional NMR spectroscopy. Secondary structure analysis, derived from several sets of spectroscopic data, shows that the domain is composed of eight antiparallel beta-strands with six interconnecting loops that fits the "type II" topology for C2 domains. Using a total of 2370 distance and torsional restraints, the structure was found to be a beta-sandwich in the "Greek key" motif. The solution structure of cPLA2-C2 domain is very similar to the X-ray crystal structure of the C2 domain of phospholipase-C-delta and phylogenetic analysis clarifies the structural role of highly conserved residues. Calorimetric studies further demonstrate that cPLA2-C2 binds two Ca2+ with observed Kds of approximately 2 microM in an entropically assisted process. Moreover, regions on cPLA2-C2 interacting with membranes were identified by 15N-HSQC-spectroscopy of cPLA2-C2 in the presence of low molecular weight lipid micelles. An extended binding site was identified that binds the phosphocholine headgroup in a Ca2+-dependent manner and also interacts with proximal regions of the membrane surface. Based upon these results, a structural model is presented for the mechanism of association of cPLA2 with its membrane substrate. |
==About this Structure== | ==About this Structure== | ||
| - | 1BCI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1BCI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1BCI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phospholipase A(2)]] | [[Category: Phospholipase A(2)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Clark, J | + | [[Category: Clark, J D.]] |
| - | [[Category: Cumming, D | + | [[Category: Cumming, D A.]] |
[[Category: Mcdonagh, T.]] | [[Category: Mcdonagh, T.]] | ||
| - | [[Category: Nalefski, E | + | [[Category: Nalefski, E A.]] |
| - | [[Category: Xu, G | + | [[Category: Xu, G Y.]] |
| - | [[Category: Yu, H | + | [[Category: Yu, H A.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: c2 domain]] | [[Category: c2 domain]] | ||
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[[Category: phosphocholine]] | [[Category: phosphocholine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:53:49 2008'' |
Revision as of 09:53, 21 February 2008
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C2 DOMAIN OF CYTOSOLIC PHOSPHOLIPASE A2, NMR, MINIMIZED AVERAGE STRUCTURE
Overview
The amino-terminal, 138 amino acid C2 domain of cytosolic phospholipase A2 (cPLA2-C2) mediates an initial step in the production of lipid mediators of inflammation: the Ca2+-dependent translocation of the enzyme to intracellular membranes with subsequent liberation of arachidonic acid. The high resolution solution structure of this Ca2+-dependent, lipid-binding domain (CaLB) has been determined using heteronuclear three-dimensional NMR spectroscopy. Secondary structure analysis, derived from several sets of spectroscopic data, shows that the domain is composed of eight antiparallel beta-strands with six interconnecting loops that fits the "type II" topology for C2 domains. Using a total of 2370 distance and torsional restraints, the structure was found to be a beta-sandwich in the "Greek key" motif. The solution structure of cPLA2-C2 domain is very similar to the X-ray crystal structure of the C2 domain of phospholipase-C-delta and phylogenetic analysis clarifies the structural role of highly conserved residues. Calorimetric studies further demonstrate that cPLA2-C2 binds two Ca2+ with observed Kds of approximately 2 microM in an entropically assisted process. Moreover, regions on cPLA2-C2 interacting with membranes were identified by 15N-HSQC-spectroscopy of cPLA2-C2 in the presence of low molecular weight lipid micelles. An extended binding site was identified that binds the phosphocholine headgroup in a Ca2+-dependent manner and also interacts with proximal regions of the membrane surface. Based upon these results, a structural model is presented for the mechanism of association of cPLA2 with its membrane substrate.
About this Structure
1BCI is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.
Reference
Solution structure and membrane interactions of the C2 domain of cytosolic phospholipase A2., Xu GY, McDonagh T, Yu HA, Nalefski EA, Clark JD, Cumming DA, J Mol Biol. 1998 Jul 17;280(3):485-500. PMID:9665851
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