5n2x: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Thermolysin in complex with inhibitor JC272== | ==Thermolysin in complex with inhibitor JC272== | ||
<StructureSection load='5n2x' size='340' side='right' caption='[[5n2x]], [[Resolution|resolution]] 1.21Å' scene=''> | <StructureSection load='5n2x' size='340' side='right'caption='[[5n2x]], [[Resolution|resolution]] 1.21Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5n2x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_thermoproteolyticus Bacillus thermoproteolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N2X OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5n2x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_thermoproteolyticus Bacillus thermoproteolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N2X OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5N2X FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8KN:(2~{S})-5-azanyl-2-[[(2~{S})-4-methyl-2-[[oxidanyl(phenylmethoxycarbonylaminomethyl)phosphoryl]amino]pentanoyl]amino]pentanoic+acid'>8KN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8KN:(2~{S})-5-azanyl-2-[[(2~{S})-4-methyl-2-[[oxidanyl(phenylmethoxycarbonylaminomethyl)phosphoryl]amino]pentanoyl]amino]pentanoic+acid'>8KN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thermolysin Thermolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.27 3.4.24.27] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thermolysin Thermolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.27 3.4.24.27] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5n2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n2x OCA], [http://pdbe.org/5n2x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n2x RCSB], [http://www.ebi.ac.uk/pdbsum/5n2x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n2x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 19: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5n2x" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5n2x" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 27: | Line 24: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus thermoproteolyticus]] | [[Category: Bacillus thermoproteolyticus]] | ||
[[Category: Large Structures]] | |||
[[Category: Thermolysin]] | [[Category: Thermolysin]] | ||
[[Category: Cramer, J]] | [[Category: Cramer, J]] | ||
Revision as of 14:56, 26 August 2020
Thermolysin in complex with inhibitor JC272Thermolysin in complex with inhibitor JC272
Structural highlights
Function[THER_BACTH] Extracellular zinc metalloprotease. Publication Abstract from PubMedIn lead optimization, open, solvent-exposed protein pockets are often disregarded as prospective binding sites. Because of bulk-solvent proximity, researchers are instead enticed to attach charged polar groups at inhibitor scaffolds to improve solubility and pharmacokinetic properties. It is rarely considered that solvent effects from water reorganization in the first hydration shell of protein-ligand complexes can have a significant impact on binding. We investigate the thermodynamic fingerprint of thermolysin inhibitors featuring terminal charged ammonium groups that are gradually pulled from a distal, solvent-exposed position into the flat, bowl-shaped S2' pocket. Even for the most remote attachment, costs for partial desolvation of the polar group next to the protein-solvent interface are difficult to compensate by interactions with the protein or surrounding water molecules. Through direct comparison with hydrophobic analogues, a significant 180-fold affinity loss was recorded, which questions popular strategies to attach polar ligand-solubilizing groups at the exposed terminus of substituents accommodated in flat open pockets. Paying the Price of Desolvation in Solvent-Exposed Protein Pockets: Impact of Distal Solubilizing Groups on Affinity and Binding Thermodynamics in a Series of Thermolysin Inhibitors.,Cramer J, Krimmer SG, Heine A, Klebe G J Med Chem. 2017 Jul 13;60(13):5791-5799. doi: 10.1021/acs.jmedchem.7b00490. Epub, 2017 Jun 22. PMID:28590130[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||