1qll: Difference between revisions
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< | ==Piratoxin-II (Prtx-II) - a K49 PLA2 from Bothrops pirajai== | ||
<StructureSection load='1qll' size='340' side='right'caption='[[1qll]], [[Resolution|resolution]] 2.04Å' scene=''> | |||
You may | == Structural highlights == | ||
or the | <table><tr><td colspan='2'>[[1qll]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_pirajai Bothrops pirajai]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QLL FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.04Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TDA:N-TRIDECANOIC+ACID'>TDA</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qll OCA], [https://pdbe.org/1qll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qll RCSB], [https://www.ebi.ac.uk/pdbsum/1qll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qll ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PA2H2_BOTPI PA2H2_BOTPI] Snake venom phospholipase A2 (PLA2) homolog that lacks enzymatic activity, but has myotoxic activity and edema-inducing activities in vivo.<ref>PMID:10863008</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ql/1qll_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1qll ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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<ref>PMID:11141053</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1qll" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Bothrops pirajai]] | [[Category: Bothrops pirajai]] | ||
[[Category: Lee | [[Category: Large Structures]] | ||
[[Category: Polikarpov | [[Category: Lee W-H]] | ||
[[Category: Polikarpov I]] | |||
Latest revision as of 15:47, 13 December 2023
Piratoxin-II (Prtx-II) - a K49 PLA2 from Bothrops pirajaiPiratoxin-II (Prtx-II) - a K49 PLA2 from Bothrops pirajai
Structural highlights
FunctionPA2H2_BOTPI Snake venom phospholipase A2 (PLA2) homolog that lacks enzymatic activity, but has myotoxic activity and edema-inducing activities in vivo.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAsp49 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. 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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