View source for 5jss


==Thermolysin in complex with JC149.==
<StructureSection load='5jss' size='340' side='right'caption='[[5jss]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jss]] 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=5JSS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JSS 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]] 1.19&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NG:N~2~-[(R)-({[(BENZYLOXY)CARBONYL]AMINO}METHYL)(HYDROXY)PHOSPHORYL]-N-[(2R)-2,3,3-TRIMETHYLBUTYL]-L-LEUCINAMIDE'>6NG</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=5jss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jss OCA], [https://pdbe.org/5jss PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jss RCSB], [https://www.ebi.ac.uk/pdbsum/5jss PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jss 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 ==
A previously studied congeneric series of thermolysin inhibitors addressing the solvent-accessible S2' pocket with different hydrophobic substituents showed modulations of the surface water layers coating the protein-bound inhibitors. Increasing stabilization of water molecules resulted in an enthalpically more favorable binding signature, overall enhancing affinity. Based on this observation, we optimized the series by designing tailored P2' substituents to improve and further stabilize the surface water network. MD simulations were applied to predict the putative water pattern around the bound ligands. Subsequently, the inhibitors were synthesized and characterized by high-resolution crystallography, microcalorimetry, and surface plasmon resonance. One of the designed inhibitors established the most pronounced water network of all inhibitors tested so far, composed of several fused water polygons, and showed 50-fold affinity enhancement with respect to the original methylated parent ligand. Notably, the inhibitor forming the most perfect water network also showed significantly prolonged residence time compared to the other tested inhibitors.

Rational Design of Thermodynamic and Kinetic Binding Profiles by Optimizing Surface Water Networks Coating Protein-Bound Ligands.,Krimmer SG, Cramer J, Betz M, Fridh V, Karlsson R, Heine A, Klebe G J Med Chem. 2016 Dec 8;59(23):10530-10548. Epub 2016 Nov 30. PMID:27933956<ref>PMID:27933956</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jss" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thermolysin 3D structures|Thermolysin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus thermoproteolyticus]]
[[Category: Large Structures]]
[[Category: Cramer J]]
[[Category: Heine A]]
[[Category: Klebe G]]
[[Category: Krimmer SG]]