4mxj: Difference between revisions
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==Thermolysin in complex with UBTLN35== | |||
<StructureSection load='4mxj' size='340' side='right'caption='[[4mxj]], [[Resolution|resolution]] 1.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4mxj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_thermoproteolyticus Bacillus thermoproteolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MXJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MXJ 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]] 1.349Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2G8:P-((((BENZYLOXY)CARBONYL)AMINO)METHYL)-N-((S)-4-METHYL-1-OXO-1-(PROPYLAMINO)PENTAN-2-YL)PHOSPHONAMIDIC+ACID'>2G8</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4mxj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mxj OCA], [https://pdbe.org/4mxj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mxj RCSB], [https://www.ebi.ac.uk/pdbsum/4mxj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mxj ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/THER_BACTH THER_BACTH] Extracellular zinc metalloprotease. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Water is ubiquitously present in any biological system and has therefore to be regarded as an additional binding partner in the protein-ligand binding process. Upon complex formation, a new solvent-exposed surface is generated and water molecules from the first solvation layer will arrange around this newly formed surface. So far, the influence of such water arrangements on the ligand binding properties is unknown. In this study, the binding modes of nine congeneric phosphonamidate-type inhibitors with systematically varied, size-increasing hydrophobic P2 ' substituents (from methyl to phenylethyl) addressing the hydrophobic, solvent-exposed S2 ' pocket of thermolysin were analyzed by high-resolution crystal structures and correlated with their thermodynamic binding profiles as measured by isothermal titration calorimetry. Overall, DeltaDeltaG spreads over 7.0 kJ mol-1 , DeltaDeltaH varies by 15.8 kJ mol-1 , and -TDeltaDeltaS by 12.1 kJ mol-1 . Throughout the series, these changes correlate remarkably well with the geometric differences of water molecules arranged adjacent to the P2 ' substituents. Ligands with medium-sized P2 ' substituents exhibit highest affinities, presumably because of their optimal solvation patterns around these complexes. The addition, removal, or rearrangement of even a single methyl group can result in a strong modulation of the adjacent water network pattern shifting from enthalpy to entropy-driven binding. In conclusion, the quality of a water network assembled around a protein-ligand complex influences the enthalpy/entropy signature and can even modulate affinity to a surprising extent. | |||
Methyl, Ethyl, Propyl, Butyl: Futile But Not for Water, as the Correlation of Structure and Thermodynamic Signature Shows in a Congeneric Series of Thermolysin Inhibitors.,Krimmer SG, Betz M, Heine A, Klebe G ChemMedChem. 2014 Mar 13. doi: 10.1002/cmdc.201400013. PMID:24623396<ref>PMID:24623396</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4mxj" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thermolysin 3D structures|Thermolysin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacillus thermoproteolyticus]] | |||
[[Category: Large Structures]] | |||
[[Category: Heine A]] | |||
[[Category: Klebe G]] | |||
[[Category: Krimmer SG]] | |||