4exm

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==The crystal structure of an engineered phage lysin containing the binding domain of pesticin and the killing domain of T4-lysozyme==
==The crystal structure of an engineered phage lysin containing the binding domain of pesticin and the killing domain of T4-lysozyme==
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<StructureSection load='4exm' size='340' side='right' caption='[[4exm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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<StructureSection load='4exm' size='340' side='right'caption='[[4exm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4exm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pestis"_(lehmann_and_neumann_1896)_migula_1900 "bacillus pestis" (lehmann and neumann 1896) migula 1900]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EXM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EXM FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4exm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Yersinia_pestis Yersinia pestis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EXM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EXM FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4epi|4epi]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pst, YP_pPCP06, YPPCP1.05c, E ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=632 "Bacillus pestis" (Lehmann and Neumann 1896) Migula 1900])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4exm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4exm OCA], [https://pdbe.org/4exm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4exm RCSB], [https://www.ebi.ac.uk/pdbsum/4exm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4exm ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr>
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<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=4exm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4exm OCA], [http://pdbe.org/4exm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4exm RCSB], [http://www.ebi.ac.uk/pdbsum/4exm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4exm ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref> [https://www.uniprot.org/uniprot/Q57159_YERPE Q57159_YERPE]
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Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against Gram-positive organisms but not against Gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA and a bacterial toxin called pesticin that targets this transporter. FyuA is a beta-barrel membrane protein belonging to the family of TonB dependent transporters, whereas pesticin is a soluble protein with two domains, one that binds to FyuA and another that is structurally similar to phage T4 lysozyme. The structure of pesticin allowed us to design a phage therapy reagent comprised of the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme. This hybrid toxin kills specific Yersinia and pathogenic E. coli strains and, importantly, can evade the pesticin immunity protein (Pim) giving it a distinct advantage over pesticin. Furthermore, because FyuA is required for virulence and is more common in pathogenic bacteria, the hybrid toxin also has the advantage of targeting primarily disease-causing bacteria rather than indiscriminately eliminating natural gut flora.
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Structural engineering of a phage lysin that targets Gram-negative pathogens.,Lukacik P, Barnard TJ, Keller PW, Chaturvedi KS, Seddiki N, Fairman JW, Noinaj N, Kirby TL, Henderson JP, Steven AC, Hinnebusch BJ, Buchanan SK Proc Natl Acad Sci U S A. 2012 Jun 7. PMID:22679291<ref>PMID:22679291</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4exm" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Lysozyme]]
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[[Category: Escherichia virus T4]]
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[[Category: Barnard, T J]]
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[[Category: Large Structures]]
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[[Category: Buchanan, S K]]
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[[Category: Yersinia pestis]]
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[[Category: Fairman, J W]]
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[[Category: Barnard TJ]]
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[[Category: Lukacik, P]]
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[[Category: Buchanan SK]]
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[[Category: Noinaj, N]]
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[[Category: Fairman JW]]
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[[Category: Seddiki, N]]
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[[Category: Lukacik P]]
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[[Category: Bacterial lysin]]
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[[Category: Noinaj N]]
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[[Category: Hydrolase]]
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[[Category: Seddiki N]]
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[[Category: Toxin]]
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Current revision

The crystal structure of an engineered phage lysin containing the binding domain of pesticin and the killing domain of T4-lysozyme

PDB ID 4exm

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