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[[Image:1ovk.jpg|left|200px]]
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{{STRUCTURE_1ovk|  PDB=1ovk  |  SCENE=  }}
'''T4 Lysozyme Cavity Mutant L99A/M102Q Bound with N-Allyl-Aniline'''


==T4 Lysozyme Cavity Mutant L99A/M102Q Bound with N-Allyl-Aniline==
<StructureSection load='1ovk' size='340' side='right'caption='[[1ovk]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ovk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OVK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OVK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NYL:N-ALLYL-ANILINE'>NYL</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=1ovk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ovk OCA], [https://pdbe.org/1ovk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ovk RCSB], [https://www.ebi.ac.uk/pdbsum/1ovk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ovk ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== 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/ov/1ovk_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=1ovk ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sampling receptor flexibility is challenging for database docking. We consider a method that treats multiple flexible regions of the binding site independently, recombining them to generate different discrete conformations. This algorithm scales linearly rather than exponentially with the receptor's degrees of freedom. The method was first evaluated for its ability to identify known ligands of a hydrophobic cavity mutant of T4 lysozyme (L99A). Some 200000 molecules of the Available Chemical Directory (ACD) were docked against an ensemble of cavity conformations. Surprisingly, the enrichment of known ligands from among a much larger number of decoys in the ACD was worse than simply docking to the apo conformation alone. Large decoys, accommodated in the larger cavity conformations sampled in the ensemble, were ranked better than known small ligands. The calculation was redone with an energy correction term that considered the cost of forming the larger cavity conformations. Enrichment improved, as did the balance between high-ranking large and small ligands. In a second retrospective test, the ACD was docked against a conformational ensemble of thymidylate synthase. Compared to docking against individual enzyme conformations, the flexible receptor docking approach improved enrichment of known ligands. Including a receptor conformational energy weighting term improved enrichment further. To test the method prospectively, the ACD database was docked against another cavity mutant of lysozyme (L99A/M102Q). A total of 18 new compounds predicted to bind this polar cavity and to change its conformation were tested experimentally; 14 were found to bind. The bound structures for seven ligands were determined by X-ray crystallography. The predicted geometries of these ligands all corresponded to the observed geometries to within 0.7A RMSD or better. Significant conformational changes of the cavity were observed in all seven complexes. In five structures, part of the observed accommodations were correctly predicted; in two structures, the receptor conformational changes were unanticipated and thus never sampled. These results suggest that although sampling receptor flexibility can lead to novel ligands that would have been missed when docking a rigid structure, it is also important to consider receptor conformational energy.


==Overview==
Testing a flexible-receptor docking algorithm in a model binding site.,Wei BQ, Weaver LH, Ferrari AM, Matthews BW, Shoichet BK J Mol Biol. 2004 Apr 9;337(5):1161-82. PMID:15046985<ref>PMID:15046985</ref>
Sampling receptor flexibility is challenging for database docking. We consider a method that treats multiple flexible regions of the binding site independently, recombining them to generate different discrete conformations. This algorithm scales linearly rather than exponentially with the receptor's degrees of freedom. The method was first evaluated for its ability to identify known ligands of a hydrophobic cavity mutant of T4 lysozyme (L99A). Some 200000 molecules of the Available Chemical Directory (ACD) were docked against an ensemble of cavity conformations. Surprisingly, the enrichment of known ligands from among a much larger number of decoys in the ACD was worse than simply docking to the apo conformation alone. Large decoys, accommodated in the larger cavity conformations sampled in the ensemble, were ranked better than known small ligands. The calculation was redone with an energy correction term that considered the cost of forming the larger cavity conformations. Enrichment improved, as did the balance between high-ranking large and small ligands. In a second retrospective test, the ACD was docked against a conformational ensemble of thymidylate synthase. Compared to docking against individual enzyme conformations, the flexible receptor docking approach improved enrichment of known ligands. Including a receptor conformational energy weighting term improved enrichment further. To test the method prospectively, the ACD database was docked against another cavity mutant of lysozyme (L99A/M102Q). A total of 18 new compounds predicted to bind this polar cavity and to change its conformation were tested experimentally; 14 were found to bind. The bound structures for seven ligands were determined by X-ray crystallography. The predicted geometries of these ligands all corresponded to the observed geometries to within 0.7A RMSD or better. Significant conformational changes of the cavity were observed in all seven complexes. In five structures, part of the observed accommodations were correctly predicted; in two structures, the receptor conformational changes were unanticipated and thus never sampled. These results suggest that although sampling receptor flexibility can lead to novel ligands that would have been missed when docking a rigid structure, it is also important to consider receptor conformational energy.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1OVK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Enterobacteria_phage_t4 Enterobacteria phage t4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OVK OCA].
</div>
<div class="pdbe-citations 1ovk" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Testing a flexible-receptor docking algorithm in a model binding site., Wei BQ, Weaver LH, Ferrari AM, Matthews BW, Shoichet BK, J Mol Biol. 2004 Apr 9;337(5):1161-82. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15046985 15046985]
*[[Lysozyme 3D structures|Lysozyme 3D structures]]
[[Category: Enterobacteria phage t4]]
== References ==
[[Category: Lysozyme]]
<references/>
[[Category: Single protein]]
__TOC__
[[Category: Baase, W A.]]
</StructureSection>
[[Category: Matthews, B W.]]
[[Category: Escherichia virus T4]]
[[Category: Shoichet, B K.]]
[[Category: Large Structures]]
[[Category: Weaver, L H.]]
[[Category: Baase WA]]
[[Category: Wei, B Q.]]
[[Category: Matthews BW]]
[[Category: Bacteriolytic enzyme]]
[[Category: Shoichet BK]]
[[Category: Glycosidase]]
[[Category: Weaver LH]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 04:19:43 2008''
[[Category: Wei BQ]]

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