4dcf - Revision history

OCA at 06:53, 27 November 2024

2024-11-27T06:53:18Z

← Older revision		Revision as of 06:53, 27 November 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PA2H1_BOTBZ PA2H1_BOTBZ] Snake venom phospholipase A2 homolog that lacks enzymatic activity. Is myotoxic and displays edema-inducing activities in mouse paw (PubMed:18602430). Also displays cytotoxic activity against some cell lines, and antimicrobial activities against E.coli, C.albicans and Leishmania (PubMed:18602430). 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:24145104). 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:24145104). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (PubMed:24145104). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (PubMed:24145104). 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:24145104).<ref>PMID:18602430</ref> <ref>PMID:24145104</ref>		[https://www.uniprot.org/uniprot/PA2H1_BOTBZ PA2H1_BOTBZ] Snake venom phospholipase A2 homolog that lacks enzymatic activity. Is myotoxic and displays edema-inducing activities in mouse paw (PubMed:18602430). Also displays cytotoxic activity against some cell lines, and antimicrobial activities against E.coli, C.albicans and Leishmania (PubMed:18602430). 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:24145104). 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:24145104). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (PubMed:24145104). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (PubMed:24145104). 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:24145104).<ref>PMID:18602430</ref> <ref>PMID:24145104</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Catalytically inactive phospholipase A(2) (PLA(2)) homologues play key roles in the pathogenesis induced by snake envenomation, causing extensive tissue damage via a mechanism still unknown. Although, the amino acid residues directly involved in catalysis are conserved, the substitution of Asp49 by Arg/Lys/Gln or Ser prevents the binding of the essential calcium ion and hence these proteins are incapable of hydrolyzing phospholipids. In this work, the crystal structure of a Lys49-PLA(2) homologue from Bothrops brazili (MTX-II) was solved in two conformational states: (a) native, with Lys49 singly coordinated by the backbone oxygen atom of Val31 and (b) complexed with tetraethylene glycol (TTEG). Interestingly, the TTEG molecule was observed in two different coordination cages depending on the orientation of the nominal calcium-binding loop and of the residue Lys49. These structural observations indicate a direct role for the residue Lys49 in the functioning of a catalytically inactive PLA(2) homologue suggesting a contribution of the active site-like region in the expression of pharmacological effects such as myotoxicity and edema formation. Despite the several crystal structures of Lys49-PLA(2) homologues already determined, their biological assembly remains controversial with two possible conformations. The extended dimer with the hydrophobic channel exposed to the solvent and the compact dimer in which the active site-like region is occluded by the dimeric interface. In the MTX-II crystal packing analysis was found only the extended dimer as a possible stable quaternary arrangement.

			Crystallographic portrayal of different conformational states of a Lys49 phospholipase A(2) homologue: Insights into structural determinants for myotoxicity and dimeric configuration.,Ullah A, Souza TA, Betzel C, Murakami MT, Arni RK Int J Biol Macromol. 2012 May 11. PMID:22584077<ref>PMID:22584077</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4dcf" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:31, 14 March 2024

2024-03-14T14:31:25Z

← Older revision		Revision as of 14:31, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DCF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DCF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.7Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=4dcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcf OCA], [https://pdbe.org/4dcf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dcf RCSB], [https://www.ebi.ac.uk/pdbsum/4dcf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dcf ProSAT]</span></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=4dcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcf OCA], [https://pdbe.org/4dcf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dcf RCSB], [https://www.ebi.ac.uk/pdbsum/4dcf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dcf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/PA2H1_BOTBZ PA2H1_BOTBZ]] Snake venom phospholipase A2 homolog that lacks enzymatic activity. Is myotoxic and displays edema-inducing activities in mouse paw (PubMed:18602430). Also displays cytotoxic activity against some cell lines, and antimicrobial activities against E.coli, C.albicans and Leishmania (PubMed:18602430). 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:24145104). 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:24145104). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (PubMed:24145104). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (PubMed:24145104). 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:24145104).<ref>PMID:18602430</ref> <ref>PMID:24145104</ref>		[https://www.uniprot.org/uniprot/PA2H1_BOTBZ PA2H1_BOTBZ] Snake venom phospholipase A2 homolog that lacks enzymatic activity. Is myotoxic and displays edema-inducing activities in mouse paw (PubMed:18602430). Also displays cytotoxic activity against some cell lines, and antimicrobial activities against E.coli, C.albicans and Leishmania (PubMed:18602430). 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:24145104). 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:24145104). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (PubMed:24145104). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (PubMed:24145104). 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:24145104).<ref>PMID:18602430</ref> <ref>PMID:24145104</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Catalytically inactive phospholipase A(2) (PLA(2)) homologues play key roles in the pathogenesis induced by snake envenomation, causing extensive tissue damage via a mechanism still unknown. Although, the amino acid residues directly involved in catalysis are conserved, the substitution of Asp49 by Arg/Lys/Gln or Ser prevents the binding of the essential calcium ion and hence these proteins are incapable of hydrolyzing phospholipids. In this work, the crystal structure of a Lys49-PLA(2) homologue from Bothrops brazili (MTX-II) was solved in two conformational states: (a) native, with Lys49 singly coordinated by the backbone oxygen atom of Val31 and (b) complexed with tetraethylene glycol (TTEG). Interestingly, the TTEG molecule was observed in two different coordination cages depending on the orientation of the nominal calcium-binding loop and of the residue Lys49. These structural observations indicate a direct role for the residue Lys49 in the functioning of a catalytically inactive PLA(2) homologue suggesting a contribution of the active site-like region in the expression of pharmacological effects such as myotoxicity and edema formation. Despite the several crystal structures of Lys49-PLA(2) homologues already determined, their biological assembly remains controversial with two possible conformations. The extended dimer with the hydrophobic channel exposed to the solvent and the compact dimer in which the active site-like region is occluded by the dimeric interface. In the MTX-II crystal packing analysis was found only the extended dimer as a possible stable quaternary arrangement.

	Crystallographic portrayal of different conformational states of a Lys49 phospholipase A(2) homologue: Insights into structural determinants for myotoxicity and dimeric configuration.,Ullah A, Souza TA, Betzel C, Murakami MT, Arni RK Int J Biol Macromol. 2012 May 11. PMID:22584077<ref>PMID:22584077</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4dcf" style="background-color:#fffaf0;"></div~~>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:12, 21 September 2022

2022-09-21T08:12:07Z

← Older revision		Revision as of 08:12, 21 September 2022
Line 3:		Line 3:
	<StructureSection load='4dcf' size='340' side='right'caption='[[4dcf]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4dcf' size='340' side='right'caption='[[4dcf]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4DCF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DCF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4dcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcf OCA], [~~http~~://pdbe.org/4dcf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4dcf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4dcf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4dcf ProSAT]</span></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=4dcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcf OCA], [https://pdbe.org/4dcf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dcf RCSB], [https://www.ebi.ac.uk/pdbsum/4dcf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dcf ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[https://www.uniprot.org/uniprot/PA2H1_BOTBZ PA2H1_BOTBZ]] Snake venom phospholipase A2 homolog that lacks enzymatic activity. Is myotoxic and displays edema-inducing activities in mouse paw (PubMed:18602430). Also displays cytotoxic activity against some cell lines, and antimicrobial activities against E.coli, C.albicans and Leishmania (PubMed:18602430). 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:24145104). 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:24145104). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (PubMed:24145104). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (PubMed:24145104). 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:24145104).<ref>PMID:18602430</ref> <ref>PMID:24145104</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 24:
	[[Category: Bothrops brazili]]		[[Category: Bothrops brazili]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Arni~~, R K~~]]		[[Category: Arni RK]]
	[[Category: Betzel, C]]		[[Category: Betzel C]]
	[[Category: Murakami~~, M T~~]]		[[Category: Murakami MT]]
	[[Category: Souza~~, T A.C B~~]]		[[Category: Souza TACB]]
	[[Category: Ullah, A]]		[[Category: Ullah A]]
	~~[[Category: Hydrolase]]~~
	~~[[Category: Lys49 phospholipase]]~~
	~~[[Category: Phospholipase~~]]

OCA at 07:30, 27 March 2019

2019-03-27T07:30:13Z

← Older revision		Revision as of 07:30, 27 March 2019
Line 1:		Line 1:

	==Structure of MTX-II from Bothrops brazili==		==Structure of MTX-II from Bothrops brazili==
	<StructureSection load='4dcf' size='340' side='right' caption='[[4dcf]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4dcf' size='340' side='right'caption='[[4dcf]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DCF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DCF FirstGlance]. <br>
Line 21:		Line 21:
	</StructureSection>		</StructureSection>
	[[Category: Bothrops brazili]]		[[Category: Bothrops brazili]]
			[[Category: Large Structures]]
	[[Category: Arni, R K]]		[[Category: Arni, R K]]
	[[Category: Betzel, C]]		[[Category: Betzel, C]]

OCA at 19:12, 4 August 2016

2016-08-04T19:12:32Z

← Older revision		Revision as of 19:12, 4 August 2016
Line 1:		Line 1:

	==Structure of MTX-II from Bothrops brazili==		==Structure of MTX-II from Bothrops brazili==
	<StructureSection load='4dcf' size='340' side='right' caption='[[4dcf]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4dcf' size='340' side='right' caption='[[4dcf]], [[Resolution\|resolution]] 2.70Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DCF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DCF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dcf RCSB], [http://www.ebi.ac.uk/pdbsum/4dcf PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcf OCA], [http://pdbe.org/4dcf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dcf RCSB], [http://www.ebi.ac.uk/pdbsum/4dcf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dcf ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 14:		Line 15:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4dcf" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:01, 21 December 2014

2014-12-21T09:01:52Z

← Older revision		Revision as of 09:01, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4dcf\| PDB~~=4dcf \| ~~SCENE~~= }}		==Structure of MTX-II from Bothrops brazili==
	===~~Structure of MTX-II~~ from Bothrops brazili===		<StructureSection load='4dcf' size='340' side='right' caption='[[4dcf]], [[Resolution\|resolution]] 2.70Å' scene=''>
	~~{{ABSTRACT_PUBMED_22584077}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4dcf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_brazili Bothrops brazili]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DCF FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dcf RCSB], [http://www.ebi.ac.uk/pdbsum/4dcf PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Catalytically inactive phospholipase A(2) (PLA(2)) homologues play key roles in the pathogenesis induced by snake envenomation, causing extensive tissue damage via a mechanism still unknown. Although, the amino acid residues directly involved in catalysis are conserved, the substitution of Asp49 by Arg/Lys/Gln or Ser prevents the binding of the essential calcium ion and hence these proteins are incapable of hydrolyzing phospholipids. In this work, the crystal structure of a Lys49-PLA(2) homologue from Bothrops brazili (MTX-II) was solved in two conformational states: (a) native, with Lys49 singly coordinated by the backbone oxygen atom of Val31 and (b) complexed with tetraethylene glycol (TTEG). Interestingly, the TTEG molecule was observed in two different coordination cages depending on the orientation of the nominal calcium-binding loop and of the residue Lys49. These structural observations indicate a direct role for the residue Lys49 in the functioning of a catalytically inactive PLA(2) homologue suggesting a contribution of the active site-like region in the expression of pharmacological effects such as myotoxicity and edema formation. Despite the several crystal structures of Lys49-PLA(2) homologues already determined, their biological assembly remains controversial with two possible conformations. The extended dimer with the hydrophobic channel exposed to the solvent and the compact dimer in which the active site-like region is occluded by the dimeric interface. In the MTX-II crystal packing analysis was found only the extended dimer as a possible stable quaternary arrangement.

	~~==About this Structure==~~		Crystallographic portrayal of different conformational states of a Lys49 phospholipase A(2) homologue: Insights into structural determinants for myotoxicity and dimeric configuration.,Ullah A, Souza TA, Betzel C, Murakami MT, Arni RK Int J Biol Macromol. 2012 May 11. PMID:22584077<ref>PMID:22584077</ref>
	~~[[4dcf]] is~~ a ~~4 chain structure with sequence from [http~~:~~//en~~.~~wikipedia~~.~~org/wiki/Bothrops_brazili Bothrops brazili]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4DCF OCA].~~

	==~~Reference~~==		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~<ref group="xtra">PMID:022584077</ref>~~<references ~~group="xtra"~~/><~~references~~/>		</div>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Bothrops brazili]]		[[Category: Bothrops brazili]]
	[[Category: Arni, R K.]]		[[Category: Arni, R K]]
	[[Category: Betzel, C.]]		[[Category: Betzel, C]]
	[[Category: Murakami, M T.]]		[[Category: Murakami, M T]]
	[[Category: Souza, T A.C B.]]		[[Category: Souza, T A.C B]]
	[[Category: Ullah, A.]]		[[Category: Ullah, A]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Lys49 phospholipase]]		[[Category: Lys49 phospholipase]]
	[[Category: Phospholipase]]		[[Category: Phospholipase]]

OCA at 04:17, 12 September 2013

2013-09-12T04:17:37Z

← Older revision		Revision as of 04:17, 12 September 2013
Line 1:		Line 1:
	~~[[Image:4dcf.jpg\|left\|200px]]~~

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4dcf", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_4dcf\| PDB=4dcf \| SCENE= }}		{{STRUCTURE_4dcf\| PDB=4dcf \| SCENE= }}

	===Structure of MTX-II from Bothrops brazili===		===Structure of MTX-II from Bothrops brazili===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22584077}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 22584077 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_22584077}}		{{ABSTRACT_PUBMED_22584077}}

Line 22:		Line 7:

	==Reference==		==Reference==
	<ref group="xtra">PMID:022584077</ref><references group="xtra"/>		<ref group="xtra">PMID:022584077</ref><references group="xtra"/><references/>
	[[Category: Bothrops brazili]]		[[Category: Bothrops brazili]]
	[[Category: Arni, R K.]]		[[Category: Arni, R K.]]

OCA at 06:14, 13 June 2012

2012-06-13T06:14:46Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4dcf.jpg|left|200px]]
-The entry 4dcf is ON HOLD
+<!--
-Authors: Ullah, A., Souza, T.A.C.B., Betzel, C., Murakami, M.T., Arni, R.K.
+===Structure of MTX-II from Bothrops brazili===
-Description: Structure of MTX-II from Bothrops brazili

OCA at 07:00, 1 February 2012

2012-02-01T07:00:05Z

← Older revision		Revision as of 07:00, 1 February 2012
Line 3:		Line 3:
	The entry 4dcf is ON HOLD		The entry 4dcf is ON HOLD

	Authors: Ullah A., Souza, T.A.C.B., Betzel, C., Murakami, M.T., Arni, R.K.		Authors: Ullah, A., Souza, T.A.C.B., Betzel, C., Murakami, M.T., Arni, R.K.

	Description: Structure of MTX-II from Bothrops brazili		Description: Structure of MTX-II from Bothrops brazili

OCA: Protected "4dcf" [edit=sysop:move=sysop]

2012-01-25T06:11:35Z

Protected "4dcf" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:11, 25 January 2012
(No difference)