1qll
From Proteopedia
(New page: 200px<br /><applet load="1qll" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qll, resolution 2.04Å" /> '''PIRATOXIN-II (PRTX-I...) |
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| - | [[Image:1qll.gif|left|200px]]<br /><applet load="1qll" size=" | + | [[Image:1qll.gif|left|200px]]<br /><applet load="1qll" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1qll, resolution 2.04Å" /> | caption="1qll, resolution 2.04Å" /> | ||
'''PIRATOXIN-II (PRTX-II)-A K49 PLA2 FROM BOTHROPS PIRAJAI'''<br /> | '''PIRATOXIN-II (PRTX-II)-A K49 PLA2 FROM BOTHROPS PIRAJAI'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Asp49 plays a fundamental role in supporting catalysis by phospholipases | + | Asp49 plays a fundamental role in supporting catalysis by phospholipases A2 by coordinating the calcium ion which aids in the stabilization of the tetrahedral intermediate. In several myotoxins from the venoms of Viperidae snakes, this aspartic acid is substituted by lysine. The loss of calcium binding capacity by these mutants has become regarded as the standard explanation for their greatly reduced or nonexistent phospholipolytic activity. Here we describe the crystal structure of one such Lys49 PLA2, piratoxin-II, in which a fatty acid molecule is observed within the substrate channel. This suggests that such toxins may be active enzymes in which catalysis is interrupted at the stage of substrate release. Comparison of the present structure with other PLA2s, both active and inactive, identifies Lys122 as one of the likely causes of the increased affinity for fatty acid in Lys49 enzymes. Its interaction with the mainchain carbonyl of Cys29 is expected to lead to hyperpolarization of the peptide bond between residues 29 and 30 leading to an increased affinity for the fatty acid headgroup. This strongly bound fatty acid may serve as an anchor to secure the toxin within the membrane thus facilitating its pathological effects. |
==About this Structure== | ==About this Structure== | ||
| - | 1QLL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bothrops_pirajai Bothrops pirajai] with TDA 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:// | + | 1QLL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bothrops_pirajai Bothrops pirajai] with <scene name='pdbligand=TDA:'>TDA</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=1QLL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phospholipase A(2)]] | [[Category: Phospholipase A(2)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Lee, W | + | [[Category: Lee, W H.]] |
[[Category: Polikarpov, I.]] | [[Category: Polikarpov, I.]] | ||
[[Category: TDA]] | [[Category: TDA]] | ||
[[Category: k49 phospholipase a2 (pla2)]] | [[Category: k49 phospholipase a2 (pla2)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:41:00 2008'' |
Revision as of 12:41, 21 February 2008
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PIRATOXIN-II (PRTX-II)-A K49 PLA2 FROM BOTHROPS PIRAJAI
Overview
Asp49 plays a fundamental role in supporting catalysis by phospholipases A2 by coordinating the calcium ion which aids in the stabilization of the tetrahedral intermediate. In several myotoxins from the venoms of Viperidae snakes, this aspartic acid is substituted by lysine. The loss of calcium binding capacity by these mutants has become regarded as the standard explanation for their greatly reduced or nonexistent phospholipolytic activity. Here we describe the crystal structure of one such Lys49 PLA2, piratoxin-II, in which a fatty acid molecule is observed within the substrate channel. This suggests that such toxins may be active enzymes in which catalysis is interrupted at the stage of substrate release. Comparison of the present structure with other PLA2s, both active and inactive, identifies Lys122 as one of the likely causes of the increased affinity for fatty acid in Lys49 enzymes. Its interaction with the mainchain carbonyl of Cys29 is expected to lead to hyperpolarization of the peptide bond between residues 29 and 30 leading to an increased affinity for the fatty acid headgroup. This strongly bound fatty acid may serve as an anchor to secure the toxin within the membrane thus facilitating its pathological effects.
About this Structure
1QLL is a Single protein structure of sequence from Bothrops pirajai with as ligand. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.
Reference
Structural basis for low catalytic activity in Lys49 phospholipases A2--a hypothesis: the crystal structure of piratoxin II complexed to fatty acid., Lee WH, da Silva Giotto MT, Marangoni S, Toyama MH, Polikarpov I, Garratt RC, Biochemistry. 2001 Jan 9;40(1):28-36. PMID:11141053
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