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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] | | [https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Hydrogen bonds are key interactions determining protein-ligand binding affinity and therefore fundamental to any biological process. Unfortunately, explicit structural information about hydrogen positions and thus H-bonds in protein-ligand complexes is extremely rare and similarly the important role of water during binding remains poorly understood. Here, we report on neutron structures of trypsin determined at very high resolutions </=1.5 A in uncomplexed and inhibited state complemented by X-ray and thermodynamic data and computer simulations. Our structures show the precise geometry of H-bonds between protein and the inhibitors N-amidinopiperidine and benzamidine along with the dynamics of the residual solvation pattern. Prior to binding, the ligand-free binding pocket is occupied by water molecules characterized by a paucity of H-bonds and high mobility resulting in an imperfect hydration of the critical residue Asp189. This phenomenon likely constitutes a key factor fueling ligand binding via water displacement and helps improving our current view on water influencing protein-ligand recognition.
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| Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes.,Schiebel J, Gaspari R, Wulsdorf T, Ngo K, Sohn C, Schrader TE, Cavalli A, Ostermann A, Heine A, Klebe G Nat Commun. 2018 Sep 3;9(1):3559. doi: 10.1038/s41467-018-05769-2. PMID:30177695<ref>PMID:30177695</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 5mop" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Trypsin 3D structures|Trypsin 3D structures]] | | *[[Trypsin 3D structures|Trypsin 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |