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[[Image:1lgx.jpg|left|200px]]
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{{STRUCTURE_1lgx|  PDB=1lgx  |  SCENE=  }}
'''T4 Lysozyme Mutant L99A/M102Q Bound by 3,5-difluoroaniline'''


==T4 Lysozyme Mutant L99A/M102Q Bound by 3,5-difluoroaniline==
<StructureSection load='1lgx' size='340' side='right'caption='[[1lgx]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lgx]] 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=1LGX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LGX 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5AN:3,5-DIFLUOROANILINE'>5AN</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=1lgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lgx OCA], [https://pdbe.org/1lgx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lgx RCSB], [https://www.ebi.ac.uk/pdbsum/1lgx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lgx 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/lg/1lgx_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=1lgx ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Prediction of interaction energies between ligands and their receptors remains a major challenge for structure-based inhibitor discovery. Much effort has been devoted to developing scoring schemes that can successfully rank the affinities of a diverse set of possible ligands to a binding site for which the structure is known. To test these scoring functions, well-characterized experimental systems can be very useful. Here, mutation-created binding sites in T4 lysozyme were used to investigate how the quality of atomic charges and solvation energies affects molecular docking. Atomic charges and solvation energies were calculated for 172,118 molecules in the Available Chemicals Directory using a semi-empirical quantum mechanical approach by the program AMSOL. The database was first screened against the apolar cavity site created by the mutation Leu99Ala (L99A). Compared to the electronegativity-based charges that are widely used, the new charges and desolvation energies improved ranking of known apolar ligands, and better distinguished them from more polar isosteres that are not observed to bind. To investigate whether the new charges had predictive value, the non-polar residue Met102, which forms part of the binding site, was changed to the polar residue glutamine. The structure of the resulting Leu99Ala and Met102Gln double mutant of T4 lysozyme (L99A/M102Q) was determined and the docking calculation was repeated for the new site. Seven representative polar molecules that preferentially docked to the polar versus the apolar binding site were tested experimentally. All seven bind to the polar cavity (L99A/M102Q) but do not detectably bind to the apolar cavity (L99A). Five ligand-bound structures of L99A/M102Q were determined by X-ray crystallography. Docking predictions corresponded to the crystallographic results to within 0.4A RMSD. Improved treatment of partial atomic charges and desolvation energies in database docking appears feasible and leads to better distinction of true ligands. Simple model binding sites, such as L99A and its more polar variants, may find broad use in the development and testing of docking algorithms.


==Overview==
A model binding site for testing scoring functions in molecular docking.,Wei BQ, Baase WA, Weaver LH, Matthews BW, Shoichet BK J Mol Biol. 2002 Sep 13;322(2):339-55. PMID:12217695<ref>PMID:12217695</ref>
Prediction of interaction energies between ligands and their receptors remains a major challenge for structure-based inhibitor discovery. Much effort has been devoted to developing scoring schemes that can successfully rank the affinities of a diverse set of possible ligands to a binding site for which the structure is known. To test these scoring functions, well-characterized experimental systems can be very useful. Here, mutation-created binding sites in T4 lysozyme were used to investigate how the quality of atomic charges and solvation energies affects molecular docking. Atomic charges and solvation energies were calculated for 172,118 molecules in the Available Chemicals Directory using a semi-empirical quantum mechanical approach by the program AMSOL. The database was first screened against the apolar cavity site created by the mutation Leu99Ala (L99A). Compared to the electronegativity-based charges that are widely used, the new charges and desolvation energies improved ranking of known apolar ligands, and better distinguished them from more polar isosteres that are not observed to bind. To investigate whether the new charges had predictive value, the non-polar residue Met102, which forms part of the binding site, was changed to the polar residue glutamine. The structure of the resulting Leu99Ala and Met102Gln double mutant of T4 lysozyme (L99A/M102Q) was determined and the docking calculation was repeated for the new site. Seven representative polar molecules that preferentially docked to the polar versus the apolar binding site were tested experimentally. All seven bind to the polar cavity (L99A/M102Q) but do not detectably bind to the apolar cavity (L99A). Five ligand-bound structures of L99A/M102Q were determined by X-ray crystallography. Docking predictions corresponded to the crystallographic results to within 0.4A RMSD. Improved treatment of partial atomic charges and desolvation energies in database docking appears feasible and leads to better distinction of true ligands. Simple model binding sites, such as L99A and its more polar variants, may find broad use in the development and testing of docking algorithms.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1LGX 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=1LGX OCA].
</div>
<div class="pdbe-citations 1lgx" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
A model binding site for testing scoring functions in molecular docking., Wei BQ, Baase WA, Weaver LH, Matthews BW, Shoichet BK, J Mol Biol. 2002 Sep 13;322(2):339-55. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12217695 12217695]
*[[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 Fri May  2 23:54:25 2008''
[[Category: Wei BQ]]

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