5p2p
From Proteopedia
(New page: 200px<br /><applet load="5p2p" size="450" color="white" frame="true" align="right" spinBox="true" caption="5p2p, resolution 2.4Å" /> '''X-RAY STRUCTURE OF PH...) |
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| - | [[Image:5p2p.gif|left|200px]]<br /><applet load="5p2p" size=" | + | [[Image:5p2p.gif|left|200px]]<br /><applet load="5p2p" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="5p2p, resolution 2.4Å" /> | caption="5p2p, resolution 2.4Å" /> | ||
'''X-RAY STRUCTURE OF PHOSPHOLIPASE A2 COMPLEXED WITH A SUBSTRATE-DERIVED INHIBITOR'''<br /> | '''X-RAY STRUCTURE OF PHOSPHOLIPASE A2 COMPLEXED WITH A SUBSTRATE-DERIVED INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Phospholipases A2 play a part in a number of physiologically important | + | Phospholipases A2 play a part in a number of physiologically important cellular processes such as inflammation, blood platelet aggregation and acute hypersensitivity. These processes are all initiated by the release of arachidonic acid from cell membranes which is catalysed by intracellular phospholipases A2 and followed by conversion of arachidonic acid to prostaglandins, leukotrienes or thromboxanes. An imbalance in the production of these compounds can lead to chronic inflammatory diseases such as rheumatoid arthritis and asthma. Inhibitors of phospholipase A2 might therefore act to reduce the effects of inflammation, so structural information about the binding of phospholipase A2 to its substrates could be helpful in the design of therapeutic drugs. The three-dimensional structure is not known for any intracellular phospholipase A2, but these enzymes share significant sequence homology with secreted phospholipases, for which some of the structures have been determined. Here we report the structure of a complex between an extracellular phospholipase A2 and a competitively inhibiting substrate analogue, which reveals considerable detail about the interaction and suggests a mechanism for catalysis by this enzyme. |
==About this Structure== | ==About this Structure== | ||
| - | 5P2P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with CA and DHG as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 5P2P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=DHG:'>DHG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=5P2P OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
| - | [[Category: Dijkstra, B | + | [[Category: Dijkstra, B W.]] |
[[Category: Drenth, J.]] | [[Category: Drenth, J.]] | ||
| - | [[Category: Kalk, K | + | [[Category: Kalk, K H.]] |
| - | [[Category: Thunnissen, M | + | [[Category: Thunnissen, M M.G M.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: DHG]] | [[Category: DHG]] | ||
[[Category: hydrolase(carboxylic ester)]] | [[Category: hydrolase(carboxylic ester)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:15:40 2008'' |
Revision as of 17:15, 21 February 2008
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X-RAY STRUCTURE OF PHOSPHOLIPASE A2 COMPLEXED WITH A SUBSTRATE-DERIVED INHIBITOR
Overview
Phospholipases A2 play a part in a number of physiologically important cellular processes such as inflammation, blood platelet aggregation and acute hypersensitivity. These processes are all initiated by the release of arachidonic acid from cell membranes which is catalysed by intracellular phospholipases A2 and followed by conversion of arachidonic acid to prostaglandins, leukotrienes or thromboxanes. An imbalance in the production of these compounds can lead to chronic inflammatory diseases such as rheumatoid arthritis and asthma. Inhibitors of phospholipase A2 might therefore act to reduce the effects of inflammation, so structural information about the binding of phospholipase A2 to its substrates could be helpful in the design of therapeutic drugs. The three-dimensional structure is not known for any intracellular phospholipase A2, but these enzymes share significant sequence homology with secreted phospholipases, for which some of the structures have been determined. Here we report the structure of a complex between an extracellular phospholipase A2 and a competitively inhibiting substrate analogue, which reveals considerable detail about the interaction and suggests a mechanism for catalysis by this enzyme.
About this Structure
5P2P is a Single protein structure of sequence from Sus scrofa with and as ligands. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.
Reference
X-ray structure of phospholipase A2 complexed with a substrate-derived inhibitor., Thunnissen MM, Ab E, Kalk KH, Drenth J, Dijkstra BW, Kuipers OP, Dijkman R, de Haas GH, Verheij HM, Nature. 1990 Oct 18;347(6294):689-91. PMID:2215698
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