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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[3n21]] 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=3N21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N21 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3n21]] 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=3N21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N21 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 1.87Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ms3|3ms3]], [[3msa|3msa]], [[3msf|3msf]], [[3msn|3msn]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</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'>[https://en.wikipedia.org/wiki/Thermolysin Thermolysin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.27 3.4.24.27] </span></td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3n21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n21 OCA], [https://pdbe.org/3n21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n21 RCSB], [https://www.ebi.ac.uk/pdbsum/3n21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n21 ProSAT]</span></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=3n21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n21 OCA], [https://pdbe.org/3n21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n21 RCSB], [https://www.ebi.ac.uk/pdbsum/3n21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n21 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/THER_BACTH THER_BACTH]] Extracellular zinc metalloprotease.
| + | [https://www.uniprot.org/uniprot/THER_BACTH THER_BACTH] Extracellular zinc metalloprotease. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Small highly soluble probe molecules such as aniline, urea, N-methylurea, 2-bromoacetate, 1,2-propanediol, nitrous oxide, benzamidine, and phenol were soaked into crystals of various proteins to map their binding pockets and to detect hot spots of binding with respect to hydrophobic and hydrophilic properties. The selected probe molecules were first tested at the zinc protease thermolysin. They were then applied to a wider range of proteins such as protein kinase A, D-xylose isomerase, 4-diphosphocytidyl-2C-methyl-D-erythritol synthase, endothiapepsin, and secreted aspartic protease 2. The crystal structures obtained clearly show that the probe molecules populate the protein binding pockets in an ordered fashion. The thus characterized, experimentally observed hot spots of binding were subjected to computational active site mapping using HotspotsX. This approach uses knowledge-based pair potentials to detect favorable binding positions for various atom types. Good agreement between the in silico hot spot predictions and the experimentally observed positions of the polar hydrogen bond forming functional groups and hydrophobic portions was obtained. Finally, we compared the observed poses of the small-molecule probes with those of much larger structurally related ligands. They coincide remarkably well with the larger ligands, considering their spatial orientation and the experienced interaction patterns. This observation confirms the fundamental hypothesis of fragment-based lead discovery: that binding poses, even of very small molecular probes, do not significantly deviate or move once a ligand is grown further into the binding site. This underscores the fact that these probes populate given hot spots and can be regarded as relevant seeds for further design.
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| - | Experimental and Computational Active Site Mapping as a Starting Point to Fragment-Based Lead Discovery.,Behnen J, Koster H, Neudert G, Craan T, Heine A, Klebe G ChemMedChem. 2011 Dec 23. doi: 10.1002/cmdc.201100490. PMID:22213702<ref>PMID:22213702</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 3n21" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Thermolysin 3D structures|Thermolysin 3D structures]] | | *[[Thermolysin 3D structures|Thermolysin 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Bacillus thermoproteolyticus]] | | [[Category: Bacillus thermoproteolyticus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thermolysin]]
| + | [[Category: Behnen J]] |
| - | [[Category: Behnen, J]] | + | [[Category: Heine A]] |
| - | [[Category: Heine, A]] | + | [[Category: Klebe G]] |
| - | [[Category: Klebe, G]] | + | |
| - | [[Category: 2-propandiol]]
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| - | [[Category: Fragment based lead discovery]]
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| - | [[Category: Fragment soaking]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Metal-binding]]
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| - | [[Category: Metalloprotease]]
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| - | [[Category: Protease]]
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| - | [[Category: S-1]]
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| - | [[Category: Secreted]]
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| - | [[Category: Zymogen]]
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