1s8h
From Proteopedia
(New page: 200px<br /><applet load="1s8h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s8h, resolution 1.80Å" /> '''Crystal structure of...) |
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| - | [[Image:1s8h.jpg|left|200px]]<br /><applet load="1s8h" size=" | + | [[Image:1s8h.jpg|left|200px]]<br /><applet load="1s8h" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1s8h, resolution 1.80Å" /> | caption="1s8h, resolution 1.80Å" /> | ||
'''Crystal structure of Lys49-Phospholipase A2 from Agkistrodon contortrix laticinctus, first fatty acid free form'''<br /> | '''Crystal structure of Lys49-Phospholipase A2 from Agkistrodon contortrix laticinctus, first fatty acid free form'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Agkistrodon contortrix laticinctus myotoxin is a Lys(49)-phospholipase | + | Agkistrodon contortrix laticinctus myotoxin is a Lys(49)-phospholipase A(2) (EC 3.1.1.4) isolated from the venom of the serpent A. contortrix laticinctus (broad-banded copperhead). We present here three monomeric crystal structures of the myotoxin, obtained under different crystallization conditions. The three forms present notable structural differences and reveal that the presence of a ligand in the active site (naturally presumed to be a fatty acid) induces the exposure of a hydrophobic surface (the hydrophobic knuckle) toward the C terminus. The knuckle in A. contortrix laticinctus myotoxin involves the side chains of Phe(121) and Phe(124) and is a consequence of the formation of a canonical structure for the main chain within the region of residues 118-125. Comparison with other Lys(49)-phospholipase A(2) myotoxins shows that although the knuckle is a generic structural motif common to all members of the family, it is not readily recognizable by simple sequence analyses. An activation mechanism is proposed that relates fatty acid retention at the active site to conformational changes within the C-terminal region, a part of the molecule that has long been associated with Ca(2+)-independent membrane damaging activity and myotoxicity. This provides, for the first time, a direct structural connection between the phospholipase "active site" and the C-terminal "myotoxic site," justifying the otherwise enigmatic conservation of the residues of the former in supposedly catalytically inactive molecules. |
==About this Structure== | ==About this Structure== | ||
| - | 1S8H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Agkistrodon_contortrix_laticinctus Agkistrodon contortrix laticinctus] with SO4 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:// | + | 1S8H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Agkistrodon_contortrix_laticinctus Agkistrodon contortrix laticinctus] with <scene name='pdbligand=SO4:'>SO4</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=1S8H OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phospholipase A(2)]] | [[Category: Phospholipase A(2)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ambrosio, A | + | [[Category: Ambrosio, A L.B.]] |
| - | [[Category: Araujo, H | + | [[Category: Araujo, H S.Selistre de.]] |
| - | [[Category: Garratt, R | + | [[Category: Garratt, R C.]] |
| - | [[Category: Nonato, M | + | [[Category: Nonato, M C.]] |
| - | [[Category: Ownby, C | + | [[Category: Ownby, C L.]] |
| - | [[Category: Souza, D | + | [[Category: Souza, D H.F de.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: fatty acid free form]] | [[Category: fatty acid free form]] | ||
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[[Category: snake venom]] | [[Category: snake venom]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:10 2008'' |
Revision as of 12:59, 21 February 2008
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Crystal structure of Lys49-Phospholipase A2 from Agkistrodon contortrix laticinctus, first fatty acid free form
Overview
Agkistrodon contortrix laticinctus myotoxin is a Lys(49)-phospholipase A(2) (EC 3.1.1.4) isolated from the venom of the serpent A. contortrix laticinctus (broad-banded copperhead). We present here three monomeric crystal structures of the myotoxin, obtained under different crystallization conditions. The three forms present notable structural differences and reveal that the presence of a ligand in the active site (naturally presumed to be a fatty acid) induces the exposure of a hydrophobic surface (the hydrophobic knuckle) toward the C terminus. The knuckle in A. contortrix laticinctus myotoxin involves the side chains of Phe(121) and Phe(124) and is a consequence of the formation of a canonical structure for the main chain within the region of residues 118-125. Comparison with other Lys(49)-phospholipase A(2) myotoxins shows that although the knuckle is a generic structural motif common to all members of the family, it is not readily recognizable by simple sequence analyses. An activation mechanism is proposed that relates fatty acid retention at the active site to conformational changes within the C-terminal region, a part of the molecule that has long been associated with Ca(2+)-independent membrane damaging activity and myotoxicity. This provides, for the first time, a direct structural connection between the phospholipase "active site" and the C-terminal "myotoxic site," justifying the otherwise enigmatic conservation of the residues of the former in supposedly catalytically inactive molecules.
About this Structure
1S8H is a Single protein structure of sequence from Agkistrodon contortrix laticinctus with as ligand. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.
Reference
A molecular mechanism for Lys49-phospholipase A2 activity based on ligand-induced conformational change., Ambrosio AL, Nonato MC, de Araujo HS, Arni R, Ward RJ, Ownby CL, de Souza DH, Garratt RC, J Biol Chem. 2005 Feb 25;280(8):7326-35. Epub 2004 Dec 13. PMID:15596433
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