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2lvz

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Revision as of 10:54, 19 May 2021

Solution structure of a Eosinophil Cationic Protein-trisaccharide heparin mimetic complex

Structural highlights

2lvz is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	RNASE3, ECP, RNS3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ECP_HUMAN] Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarization of preferentially Gram-negative, but also Gram-positive strains. Promotes E.coli outer membrane detachment, alteration of the overall cell shape and partial loss of cell content.^[1] ^[2]

Publication Abstract from PubMed

Protein-glycosaminoglycan interactions are essential in many biological processes and human diseases, yet how their recognition occurs is poorly understood. Eosinophil cationic protein (ECP) is a cytotoxic ribonuclease that interacts with glycosaminoglycans at the cell surface; this promotes the destabilization of the cellular membrane and triggers ECP's toxic activity. To understand this membrane destabilization event and the differences in the toxicity of ECP and its homologues, the high resolution solution structure of the complex between full length folded ECP and a heparin-derived trisaccharide (O-iPr-alpha-D-GlcNS6S-alpha(1-4)-L-IdoA2S-alpha(1-4)-D-GlcNS6S) has been solved by NMR methods and molecular dynamics simulations. The bound protein retains the tertiary structure of the free protein. The (2)S(0) conformation of the IdoA ring is preferably recognized by the protein. We have identified the precise location of the heparin binding site, dissected the specific interactions responsible for molecular recognition, and defined the structural requirements for this interaction. The structure reveals the contribution of Arg7, Gln14, and His15 in helix alpha1, Gln40 in strand beta1, His64 in loop 4, and His128 in strand beta6 in the recognition event and corroborates the previously reported participation of residues Arg34-Asn39. The participation of the catalytic triad (His15, Lys38, His128) in recognizing the heparin mimetic reveals, at atomic resolution, the mechanism of heparin's inhibition of ECP's ribonucleolytic activity. We have integrated all the available data to propose a molecular model for the membrane interaction process. The solved NMR complex provides the structural model necessary to design inhibitors to block ECP's toxicity implicated in eosinophil pathologies.

Insights into the glycosaminoglycan-mediated cytotoxic mechanism of eosinophil cationic protein revealed by NMR.,Garcia-Mayoral MF, Canales A, Diaz D, Lopez-Prados J, Moussaoui M, de Paz JL, Angulo J, Nieto PM, Jimenez-Barbero J, Boix E, Bruix M ACS Chem Biol. 2013 Jan 18;8(1):144-51. doi: 10.1021/cb300386v. Epub 2012 Oct 9. PMID:23025322^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF. Antibiotic proteins of human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5610-4. PMID:2501794
↑ Torrent M, de la Torre BG, Nogues VM, Andreu D, Boix E. Bactericidal and membrane disruption activities of the eosinophil cationic protein are largely retained in an N-terminal fragment. Biochem J. 2009 Jul 15;421(3):425-34. doi: 10.1042/BJ20082330. PMID:19450231 doi:10.1042/BJ20082330
↑ Garcia-Mayoral MF, Canales A, Diaz D, Lopez-Prados J, Moussaoui M, de Paz JL, Angulo J, Nieto PM, Jimenez-Barbero J, Boix E, Bruix M. Insights into the glycosaminoglycan-mediated cytotoxic mechanism of eosinophil cationic protein revealed by NMR. ACS Chem Biol. 2013 Jan 18;8(1):144-51. doi: 10.1021/cb300386v. Epub 2012 Oct 9. PMID:23025322 doi:10.1021/cb300386v

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lvz"

@@ Line 1: / Line 1: @@
 ==Solution structure of a Eosinophil Cationic Protein-trisaccharide heparin mimetic complex==
-<StructureSection load='2lvz' size='340' side='right' caption='[[2lvz]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2lvz' size='340' side='right'caption='[[2lvz]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2lvz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LVZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LVZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2lvz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LVZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LVZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=LVZ:PROPAN-2-YL+2-DEOXY-6-O-SULFO-2-(SULFOAMINO)-ALPHA-D-GLUCOPYRANOSIDE'>LVZ</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=LVZ:PROPAN-2-YL+2-DEOXY-6-O-SULFO-2-(SULFOAMINO)-ALPHA-D-GLUCOPYRANOSIDE'>LVZ</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNASE3, ECP, RNS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNASE3, ECP, RNS3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2lvz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lvz OCA], [http://pdbe.org/2lvz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lvz RCSB], [http://www.ebi.ac.uk/pdbsum/2lvz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lvz 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=2lvz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lvz OCA], [https://pdbe.org/2lvz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lvz RCSB], [https://www.ebi.ac.uk/pdbsum/2lvz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lvz ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ECP_HUMAN ECP_HUMAN]] Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarization of preferentially Gram-negative, but also Gram-positive strains. Promotes E.coli outer membrane detachment, alteration of the overall cell shape and partial loss of cell content.<ref>PMID:2501794</ref> <ref>PMID:19450231</ref>
+[[https://www.uniprot.org/uniprot/ECP_HUMAN ECP_HUMAN]] Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarization of preferentially Gram-negative, but also Gram-positive strains. Promotes E.coli outer membrane detachment, alteration of the overall cell shape and partial loss of cell content.<ref>PMID:2501794</ref> <ref>PMID:19450231</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Angulo, J]]
 [[Category: Barbero, J Jimenez]]

2lvz

From Proteopedia

Revision as of 10:54, 19 May 2021

Solution structure of a Eosinophil Cationic Protein-trisaccharide heparin mimetic complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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