1z76
From Proteopedia
(New page: 200px<br /><applet load="1z76" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z76, resolution 1.85Å" /> '''Crystal structure of...) |
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| - | [[Image:1z76.gif|left|200px]]<br /><applet load="1z76" size=" | + | [[Image:1z76.gif|left|200px]]<br /><applet load="1z76" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1z76, resolution 1.85Å" /> | caption="1z76, resolution 1.85Å" /> | ||
'''Crystal structure of an acidic phospholipase A2 (BthA-I) from Bothrops jararacussu venom complexed with p-bromophenacyl bromide'''<br /> | '''Crystal structure of an acidic phospholipase A2 (BthA-I) from Bothrops jararacussu venom complexed with p-bromophenacyl bromide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of an acidic phospholipase A(2) isolated from | + | The crystal structure of an acidic phospholipase A(2) isolated from Bothrops jararacussu venom (BthA-I) chemically modified with p-bromophenacyl bromide (BPB) has been determined at 1.85 Angstroms resolution. The catalytic, platelet-aggregation inhibition, anticoagulant and hypotensive activities of BthA-I are abolished by ligand binding. Electron-density maps permitted unambiguous identification of inhibitor covalently bound to His48 in the substrate-binding cleft. The BthA-I-BPB complex contains three structural regions that are modified after inhibitor binding: the Ca(2+)-binding loop, beta-wing and C-terminal regions. Comparison of BthA-I-BPB with two other BPB-inhibited PLA(2) structures suggests that in the absence of Na(+) ions at the Ca(2+)-binding loop, this loop and other regions of the PLA(2)s undergo structural changes. The BthA-I-BPB structure reveals a novel oligomeric conformation. This conformation is more energetically and conformationally stable than the native structure and the abolition of pharmacological activities by the ligand may be related to the oligomeric structural changes. A residue of the ;pancreatic' loop (Lys69), which is usually attributed as providing the anticoagulant effect, is in the dimeric interface of BthA-I-BPB, leading to a new hypothesis regarding the abolition of this activity by BPB. |
==About this Structure== | ==About this Structure== | ||
| - | 1Z76 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu] with PBP 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:// | + | 1Z76 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu] with <scene name='pdbligand=PBP:'>PBP</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=1Z76 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phospholipase A(2)]] | [[Category: Phospholipase A(2)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fontes, M | + | [[Category: Fontes, M R.]] |
| - | [[Category: Magro, A | + | [[Category: Magro, A J.]] |
| - | [[Category: Soares, A | + | [[Category: Soares, A M.]] |
| - | [[Category: Takeda, A | + | [[Category: Takeda, A A.]] |
[[Category: PBP]] | [[Category: PBP]] | ||
[[Category: acidic phospholipase a2]] | [[Category: acidic phospholipase a2]] | ||
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[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:45 2008'' |
Revision as of 14:12, 21 February 2008
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Crystal structure of an acidic phospholipase A2 (BthA-I) from Bothrops jararacussu venom complexed with p-bromophenacyl bromide
Overview
The crystal structure of an acidic phospholipase A(2) isolated from Bothrops jararacussu venom (BthA-I) chemically modified with p-bromophenacyl bromide (BPB) has been determined at 1.85 Angstroms resolution. The catalytic, platelet-aggregation inhibition, anticoagulant and hypotensive activities of BthA-I are abolished by ligand binding. Electron-density maps permitted unambiguous identification of inhibitor covalently bound to His48 in the substrate-binding cleft. The BthA-I-BPB complex contains three structural regions that are modified after inhibitor binding: the Ca(2+)-binding loop, beta-wing and C-terminal regions. Comparison of BthA-I-BPB with two other BPB-inhibited PLA(2) structures suggests that in the absence of Na(+) ions at the Ca(2+)-binding loop, this loop and other regions of the PLA(2)s undergo structural changes. The BthA-I-BPB structure reveals a novel oligomeric conformation. This conformation is more energetically and conformationally stable than the native structure and the abolition of pharmacological activities by the ligand may be related to the oligomeric structural changes. A residue of the ;pancreatic' loop (Lys69), which is usually attributed as providing the anticoagulant effect, is in the dimeric interface of BthA-I-BPB, leading to a new hypothesis regarding the abolition of this activity by BPB.
About this Structure
1Z76 is a Single protein structure of sequence from Bothrops jararacussu with as ligand. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.
Reference
Structure of BthA-I complexed with p-bromophenacyl bromide: possible correlations with lack of pharmacological activity., Magro AJ, Takeda AA, Soares AM, Fontes MR, Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1670-7. Epub 2005, Nov 19. PMID:16301802
Page seeded by OCA on Thu Feb 21 16:12:45 2008
Categories: Bothrops jararacussu | Phospholipase A(2) | Single protein | Fontes, M R. | Magro, A J. | Soares, A M. | Takeda, A A. | PBP | Acidic phospholipase a2 | Bothrops jararacussu venom | Crystal structure | Dimeric phospholipase a2 | Oligomeric state | P-bromophenacyl bromide | Phospholipase a2 inhibition | Platelet aggregation and hypotensive effects | X-ray crystallography
