4idj

From Proteopedia

(Difference between revisions)

Revision as of 10:32, 5 August 2016

S.Aureus a-hemolysin monomer in complex with Fab

Structural highlights

4idj is a 3 chain structure with sequence from "micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	hla, hly ("Micrococcus aureus" (Rosenbach 1884) Zopf 1885)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HLA_STAAU] Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity.

Publication Abstract from PubMed

The emergence and spread of multi-drug-resistant strains of Staphylococcus aureus in hospitals and in the community emphasize the urgency for the development of novel therapeutic interventions. Our approach was to evaluate the potential of harnessing the human immune system to guide the development of novel therapeutics. We explored the role of preexisting antibodies against S. aureus alpha-hemolysin in the serum of human individuals by isolating and characterizing one antibody with a remarkably high affinity to alpha-hemolysin. The antibody provided protection in S. aureus pneumonia, skin, and bacteremia mouse models of infection and also showed therapeutic efficacy when dosed up to 18 h post-infection in the pneumonia model. Additionally, in pneumonia and bacteremia animal models, the therapeutic efficacy of the alpha-hemolysin antibody appeared additive to the antibiotic linezolid. To better understand the mechanism of action of this isolated antibody, we solved the crystal structure of the alpha-hemolysin:antibody complex. To our knowledge, this is the first report of the crystal structure of the alpha-hemolysin monomer. The structure of the complex shows that the antibody binds alpha-hemolysin between the cap and the rim domains. In combination with biochemical data, the structure suggests that the antibody neutralizes the activity of the toxin by preventing binding to the plasma membrane of susceptible host cells. The data presented here suggest that protective antibodies directed against S. aureus molecules exist in some individuals and that such antibodies have a therapeutic potential either alone or in combination with antibiotics.

Mechanism of action and in vivo efficacy of a human-derived antibody against Staphylococcus aureus alpha-hemolysin.,Foletti D, Strop P, Shaughnessy L, Hasa-Moreno A, Casas MG, Russell M, Bee C, Wu S, Pham A, Zeng Z, Pons J, Rajpal A, Shelton D J Mol Biol. 2013 May 27;425(10):1641-54. doi: 10.1016/j.jmb.2013.02.008. Epub, 2013 Feb 13. PMID:23416200^[1]

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

References

↑ Foletti D, Strop P, Shaughnessy L, Hasa-Moreno A, Casas MG, Russell M, Bee C, Wu S, Pham A, Zeng Z, Pons J, Rajpal A, Shelton D. Mechanism of action and in vivo efficacy of a human-derived antibody against Staphylococcus aureus alpha-hemolysin. J Mol Biol. 2013 May 27;425(10):1641-54. doi: 10.1016/j.jmb.2013.02.008. Epub, 2013 Feb 13. PMID:23416200 doi:10.1016/j.jmb.2013.02.008

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4idj"

@@ Line 1: / Line 1: @@
 ==S.Aureus a-hemolysin monomer in complex with Fab==
 <StructureSection load='4idj' size='340' side='right' caption='[[4idj]], [[Resolution|resolution]] 3.36&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4idj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IDJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IDJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4idj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IDJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IDJ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hla, hly ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hla, hly ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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=4idj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4idj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4idj RCSB], [http://www.ebi.ac.uk/pdbsum/4idj 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=4idj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4idj OCA], [http://pdbe.org/4idj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4idj RCSB], [http://www.ebi.ac.uk/pdbsum/4idj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4idj ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4idj" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
-[[Category: Staphylococcus aureus]]
 [[Category: Strop, P]]
 [[Category: Cytolytic protein]]

4idj

From Proteopedia

Revision as of 10:32, 5 August 2016

S.Aureus a-hemolysin monomer in complex with Fab

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox