This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3hzw

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:34, 6 September 2023) (edit) (undo)
 
(10 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:3hzw.png|left|200px]]
 
-
<!--
+
==Crystal structure of bothropstoxin-I chemically modified by p-bromophenacyl bromide (BPB)==
-
The line below this paragraph, containing "STRUCTURE_3hzw", creates the "Structure Box" on the page.
+
<StructureSection load='3hzw' size='340' side='right'caption='[[3hzw]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[3hzw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HZW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HZW FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.28&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=PBP:1-(4-BROMO-PHENYL)-ETHANONE'>PBP</scene></td></tr>
-
{{STRUCTURE_3hzw| PDB=3hzw | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hzw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hzw OCA], [https://pdbe.org/3hzw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hzw RCSB], [https://www.ebi.ac.uk/pdbsum/3hzw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hzw ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/PA2H1_BOTJR PA2H1_BOTJR] Snake venom phospholipase A2 homolog that lacks enzymatic activity. Shows local myotoxic activity (PubMed:11018293, PubMed:12079495, PubMed:31906173). Induces inflammation, since it induces edema and leukocytes infiltration (PubMed:11018293, PubMed:31906173). In addition, it induces NLRP3 NLRP3, ASC (PYCARD), caspase-1 (CASP1), and IL-1beta (IL1B) gene expression in the gastrocnemius muscle, showing that it is able to activate NLRP3 inflammasome (PubMed:31906173). It also damages artificial and myoblast membranes by a calcium-independent mechanism, has bactericidal activity, and induces neuromuscular blockade (PubMed:27531710). A model of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated by the entrance of a hydrophobic molecule (e.g. fatty acid) at the hydrophobic channel of the protein leading to a reorientation of a monomer (PubMed:27531710) (By similarity). This reorientation causes a transition between 'inactive' to 'active' states, causing alignment of C-terminal and membrane-docking sites (MDoS) side-by-side and putting the membrane-disruption sites (MDiS) in the same plane, exposed to solvent and in a symmetric position for both monomers (PubMed:27531710) (By similarity). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (PubMed:27531710) (By similarity). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (PubMed:27531710) (By similarity). This insertion causes a disorganization of the membrane, allowing an uncontrolled influx of ions (i.e. calcium and sodium), and eventually triggering irreversible intracellular alterations and cell death (PubMed:27531710) (By similarity).[UniProtKB:I6L8L6]<ref>PMID:11018293</ref> <ref>PMID:11829743</ref> <ref>PMID:12079495</ref> <ref>PMID:17157889</ref> <ref>PMID:17346668</ref> <ref>PMID:18160090</ref> <ref>PMID:27531710</ref> <ref>PMID:3176051</ref> <ref>PMID:31906173</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/hz/3hzw_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=3hzw ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Phospholipases A(2) (Asp49-PLA(2)s) are enzymes responsible for cellular membrane disruption through Ca(2+)-dependent hydrolysis of phospholipids. A class of these proteins (Lys49-PLA(2)s) does not show catalytic activity but can exert a pronounced local myotoxic effect that is not neutralized by serum therapy. In this work, we present five structures of Lys49-PLA(2)s from snakes of the Bothrops genus in apo form, complexed with PEG molecules and chemically modified by p-bromofenacil bromide (BPB), a classic inhibitor of PLA(2). We present herein an extensive structural analysis including: (i) the function of hydrophobic long-chain molecules as Lys49-PLA(2)s inhibitors, (ii) the role of Lys122, previously indicated as being responsible for Lys49-PLA(2)s catalytic inactivity and, (iii) a structural comparison of the Ca(2+)-binding loop region between Lys49 and Asp49-PLA(2)s. The Lys122 analysis of 30 different monomers for apo and complexed Lys49-PLA(2)s structures shows that this residue is very flexible and may bind to different carboxyl groups giving stability to the crystal structures. The structural comparisons of the Ca(2+)-binding loop region between Lys49 and Asp49-PLA(2)s reveal the importance of the Tyr28 residue conservation in Asp49-PLA(2)s to the integrity of this loop. The Tyr28 residue stabilizes this region by an interaction with Gly35 residue. In Lys49-PLA(2)s and low-catalytic Asp49-PLA(2)s this interaction does not occur, preventing the binding of Ca(2+).
-
===Crystal structure of bothropstoxin-I chemically modified by p-bromophenacyl bromide (BPB)===
+
Comparison between apo and complexed structures of bothropstoxin-I reveals the role of Lys122 and Ca(2+)-binding loop region for the catalytically inactive Lys49-PLA(2)s.,Fernandes CA, Marchi-Salvador DP, Salvador GM, Silva MC, Costa TR, Soares AM, Fontes MR J Struct Biol. 2010 Apr 4. PMID:20371382<ref>PMID:20371382</ref>
-
 
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
<!--
+
</div>
-
The line below this paragraph, {{ABSTRACT_PUBMED_20371382}}, adds the Publication Abstract to the page
+
<div class="pdbe-citations 3hzw" style="background-color:#fffaf0;"></div>
-
(as it appears on PubMed at http://www.pubmed.gov), where 20371382 is the PubMed ID number.
+
-
-->
+
-
{{ABSTRACT_PUBMED_20371382}}
+
-
 
+
-
==About this Structure==
+
-
[[3hzw]] is a 2 chain structure of [[Phospholipase A2]] with sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HZW OCA].
+
==See Also==
==See Also==
-
*[[Phospholipase A2]]
+
*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]]
-
 
+
*[[Phospholipase A2 homolog|Phospholipase A2 homolog]]
-
==Reference==
+
== References ==
-
<ref group="xtra">PMID:20371382</ref><references group="xtra"/>
+
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Bothrops jararacussu]]
[[Category: Bothrops jararacussu]]
-
[[Category: Fernandes, C A.H.]]
+
[[Category: Large Structures]]
-
[[Category: Fontes, M R.M.]]
+
[[Category: Fernandes CAH]]
-
[[Category: Marchi-Salvador, D P.]]
+
[[Category: Fontes MRM]]
-
[[Category: Soares, A M.]]
+
[[Category: Marchi-Salvador DP]]
-
[[Category: Antibiotic]]
+
[[Category: Soares AM]]
-
[[Category: Antimicrobial]]
+
-
[[Category: Bothropstoxin-i]]
+
-
[[Category: Disulfide bond]]
+
-
[[Category: Lys49-pla2]]
+
-
[[Category: Myotoxicity]]
+
-
[[Category: Myotoxin]]
+
-
[[Category: P-bromophenacyl bromide]]
+
-
[[Category: Phospholipase homologue]]
+
-
[[Category: Secreted]]
+
-
[[Category: Toxin]]
+

Current revision

Crystal structure of bothropstoxin-I chemically modified by p-bromophenacyl bromide (BPB)

PDB ID 3hzw

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3hzw"
Personal tools