3htd: Difference between revisions
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< | ==(Z)-Thiophene-2-carboxaldoxime in complex with T4 lysozyme L99A/M102Q== | ||
<StructureSection load='3htd' size='340' side='right'caption='[[3htd]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3htd]] 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=3HTD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HTD 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]] 1.4Å</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=JZ5:(NZ)-N-(THIOPHEN-2-YLMETHYLIDENE)HYDROXYLAMINE'>JZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=3htd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3htd OCA], [https://pdbe.org/3htd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3htd RCSB], [https://www.ebi.ac.uk/pdbsum/3htd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3htd 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/ht/3htd_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=3htd ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We present a combined experimental and modeling study of organic ligand molecules binding to a slightly polar engineered cavity site in T4 lysozyme (L99A/M102Q). For modeling, we computed alchemical absolute binding free energies. These were blind tests performed prospectively on 13 diverse, previously untested candidate ligand molecules. We predicted that eight compounds would bind to the cavity and five would not; 11 of 13 predictions were correct at this level. The RMS error to the measurable absolute binding energies was 1.8 kcal/mol. In addition, we computed "relative" binding free energies for six phenol derivatives starting from two known ligands: phenol and catechol. The average RMS error in the relative free energy prediction was 2.5 kcal/mol (phenol) and 1.1 kcal/mol (catechol). To understand these results at atomic resolution, we obtained x-ray co-complex structures for nine of the diverse ligands and for all six phenol analogs. The average RMSD of the predicted pose to the experiment was 2.0 A (diverse set), 1.8 A (phenol-derived predictions), and 1.2 A (catechol-derived predictions). We found that predicting accurate affinities and rank-orderings required near-native starting orientations of the ligand in the binding site. Unanticipated binding modes, multiple ligand binding, and protein conformational change all proved challenging for the free energy methods. We believe that these results can help guide future improvements in physics-based absolute binding free energy methods. | |||
Predicting ligand binding affinity with alchemical free energy methods in a polar model binding site.,Boyce SE, Mobley DL, Rocklin GJ, Graves AP, Dill KA, Shoichet BK J Mol Biol. 2009 Dec 11;394(4):747-63. Epub 2009 Sep 24. PMID:19782087<ref>PMID:19782087</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3htd" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Lysozyme 3D structures|Lysozyme 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Escherichia virus T4]] | ||
[[Category: Large Structures]] | |||
[[Category: Boyce SE]] | |||
== | [[Category: Dill KA]] | ||
< | [[Category: Graves AP]] | ||
[[Category: | [[Category: Mobley DL]] | ||
[[Category: | [[Category: Rocklin GJ]] | ||
[[Category: Boyce | [[Category: Shoichet BK]] | ||
[[Category: Dill | |||
[[Category: Graves | |||
[[Category: Mobley | |||
[[Category: Rocklin | |||
[[Category: Shoichet | |||
Latest revision as of 10:30, 6 September 2023
(Z)-Thiophene-2-carboxaldoxime in complex with T4 lysozyme L99A/M102Q(Z)-Thiophene-2-carboxaldoxime in complex with T4 lysozyme L99A/M102Q
Structural highlights
FunctionENLYS_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.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe present a combined experimental and modeling study of organic ligand molecules binding to a slightly polar engineered cavity site in T4 lysozyme (L99A/M102Q). For modeling, we computed alchemical absolute binding free energies. These were blind tests performed prospectively on 13 diverse, previously untested candidate ligand molecules. We predicted that eight compounds would bind to the cavity and five would not; 11 of 13 predictions were correct at this level. The RMS error to the measurable absolute binding energies was 1.8 kcal/mol. In addition, we computed "relative" binding free energies for six phenol derivatives starting from two known ligands: phenol and catechol. The average RMS error in the relative free energy prediction was 2.5 kcal/mol (phenol) and 1.1 kcal/mol (catechol). To understand these results at atomic resolution, we obtained x-ray co-complex structures for nine of the diverse ligands and for all six phenol analogs. The average RMSD of the predicted pose to the experiment was 2.0 A (diverse set), 1.8 A (phenol-derived predictions), and 1.2 A (catechol-derived predictions). We found that predicting accurate affinities and rank-orderings required near-native starting orientations of the ligand in the binding site. Unanticipated binding modes, multiple ligand binding, and protein conformational change all proved challenging for the free energy methods. We believe that these results can help guide future improvements in physics-based absolute binding free energy methods. Predicting ligand binding affinity with alchemical free energy methods in a polar model binding site.,Boyce SE, Mobley DL, Rocklin GJ, Graves AP, Dill KA, Shoichet BK J Mol Biol. 2009 Dec 11;394(4):747-63. Epub 2009 Sep 24. PMID:19782087[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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