7l3h: Difference between revisions
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==T4 Lysozyme L99A - ethylbenzene - RT== | ==T4 Lysozyme L99A - ethylbenzene - RT== | ||
<StructureSection load='7l3h' size='340' side='right'caption='[[7l3h]]' scene=''> | <StructureSection load='7l3h' size='340' side='right'caption='[[7l3h]], [[Resolution|resolution]] 1.39Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L3H FirstGlance]. <br> | <table><tr><td colspan='2'>[[7l3h]] 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=7L3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L3H FirstGlance]. <br> | ||
</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=7l3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l3h OCA], [https://pdbe.org/7l3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l3h RCSB], [https://www.ebi.ac.uk/pdbsum/7l3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l3h ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.39Å</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=PYJ:PHENYLETHANE'>PYJ</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=7l3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l3h OCA], [https://pdbe.org/7l3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l3h RCSB], [https://www.ebi.ac.uk/pdbsum/7l3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l3h ProSAT]</span></td></tr> | |||
</table> | </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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
X-ray crystallography is the gold standard to resolve conformational ensembles that are significant for protein function, ligand discovery, and computational methods development. However, relevant conformational states may be missed at common cryogenic (cryo) data-collection temperatures but can be populated at room temperature. To assess the impact of temperature on making structural and computational discoveries, we systematically investigated protein conformational changes in response to temperature and ligand binding in a structural and computational workhorse, the T4 lysozyme L99A cavity. Despite decades of work on this protein, shifting to RT reveals new global and local structural changes. These include uncovering an apo helix conformation that is hidden at cryo but relevant for ligand binding, and altered side chain and ligand conformations. To evaluate the impact of temperature-induced protein and ligand changes on the utility of structural information in computation, we evaluated how temperature can mislead computational methods that employ cryo structures for validation. We find that when comparing simulated structures just to experimental cryo structures, hidden successes and failures often go unnoticed. When using structural information in ligand binding predictions, both coarse docking and rigorous binding free energy calculations are influenced by temperature effects. The trend that cryo artifacts limit the utility of structures for computation holds across five distinct protein classes. Our results suggest caution when consulting cryogenic structural data alone, as temperature artifacts can conceal errors and prevent successful computational predictions, which can mislead the development and application of computational methods in discovering bioactive molecules. | |||
Temperature artifacts in protein structures bias ligand-binding predictions.,Bradford SYC, El Khoury L, Ge Y, Osato M, Mobley DL, Fischer M Chem Sci. 2021 Jul 13;12(34):11275-11293. doi: 10.1039/d1sc02751d. eCollection, 2021 Sep 1. PMID:34667539<ref>PMID:34667539</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7l3h" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Lysozyme 3D structures|Lysozyme 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Escherichia virus T4]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bradford SYC]] | [[Category: Bradford SYC]] | ||
[[Category: Fischer M]] | [[Category: Fischer M]] | ||
Latest revision as of 18:36, 18 October 2023
T4 Lysozyme L99A - ethylbenzene - RTT4 Lysozyme L99A - ethylbenzene - RT
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] Publication Abstract from PubMedX-ray crystallography is the gold standard to resolve conformational ensembles that are significant for protein function, ligand discovery, and computational methods development. However, relevant conformational states may be missed at common cryogenic (cryo) data-collection temperatures but can be populated at room temperature. To assess the impact of temperature on making structural and computational discoveries, we systematically investigated protein conformational changes in response to temperature and ligand binding in a structural and computational workhorse, the T4 lysozyme L99A cavity. Despite decades of work on this protein, shifting to RT reveals new global and local structural changes. These include uncovering an apo helix conformation that is hidden at cryo but relevant for ligand binding, and altered side chain and ligand conformations. To evaluate the impact of temperature-induced protein and ligand changes on the utility of structural information in computation, we evaluated how temperature can mislead computational methods that employ cryo structures for validation. We find that when comparing simulated structures just to experimental cryo structures, hidden successes and failures often go unnoticed. When using structural information in ligand binding predictions, both coarse docking and rigorous binding free energy calculations are influenced by temperature effects. The trend that cryo artifacts limit the utility of structures for computation holds across five distinct protein classes. Our results suggest caution when consulting cryogenic structural data alone, as temperature artifacts can conceal errors and prevent successful computational predictions, which can mislead the development and application of computational methods in discovering bioactive molecules. Temperature artifacts in protein structures bias ligand-binding predictions.,Bradford SYC, El Khoury L, Ge Y, Osato M, Mobley DL, Fischer M Chem Sci. 2021 Jul 13;12(34):11275-11293. doi: 10.1039/d1sc02751d. eCollection, 2021 Sep 1. PMID:34667539[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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