guest ::
| Home > Publications database > Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes > print |
| Home > Publications database > Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes > print |
| 001 | 859974 | ||
| 005 | 20210130000429.0 | ||
| 024 | 7 | _ | |a 10.1038/s41467-018-05769-2 |2 doi |
| 024 | 7 | _ | |a 2128/21480 |2 Handle |
| 024 | 7 | _ | |a pmid:30177695 |2 pmid |
| 024 | 7 | _ | |a WOS:000443465900001 |2 WOS |
| 024 | 7 | _ | |a altmetric:47595366 |2 altmetric |
| 037 | _ | _ | |a FZJ-2019-00780 |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Schiebel, Johannes |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes |
| 260 | _ | _ | |a [London] |c 2018 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1548858195_21932 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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 Å 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. |
| 536 | _ | _ | |0 G:(DE-HGF)POF3-6G15 |f POF III |x 0 |c POF3-6G15 |a 6G15 - FRM II / MLZ (POF3-6G15) |
| 536 | _ | _ | |a 6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623) |0 G:(DE-HGF)POF3-6G4 |c POF3-623 |f POF III |x 1 |
| 536 | _ | _ | |a 6215 - Soft Matter, Health and Life Sciences (POF3-621) |0 G:(DE-HGF)POF3-6215 |c POF3-621 |f POF III |x 2 |
| 588 | _ | _ | |a Dataset connected to CrossRef |
| 650 | 2 | 7 | |a Biology |0 V:(DE-MLZ)SciArea-160 |2 V:(DE-HGF) |x 0 |
| 650 | 1 | 7 | |a Health and Life |0 V:(DE-MLZ)GC-130-2016 |2 V:(DE-HGF) |x 0 |
| 693 | _ | _ | |a Forschungs-Neutronenquelle Heinz Maier-Leibnitz |e BIODIFF: Diffractometer for large unit cells |f NL1 |1 EXP:(DE-MLZ)FRMII-20140101 |0 EXP:(DE-MLZ)BIODIFF-20140101 |5 EXP:(DE-MLZ)BIODIFF-20140101 |6 EXP:(DE-MLZ)NL1-20140101 |x 0 |
| 700 | 1 | _ | |a Gaspari, Roberto |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Wulsdorf, Tobias |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Ngo, Khang |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Sohn, Christian |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Schrader, Tobias E. |0 P:(DE-Juel1)138266 |b 5 |
| 700 | 1 | _ | |a Cavalli, Andrea |0 P:(DE-HGF)0 |b 6 |
| 700 | 1 | _ | |a Ostermann, Andreas |0 0000-0002-1477-5590 |b 7 |
| 700 | 1 | _ | |a Heine, Andreas |0 P:(DE-HGF)0 |b 8 |e Corresponding author |
| 700 | 1 | _ | |a Klebe, Gerhard |0 P:(DE-HGF)0 |b 9 |e Corresponding author |
| 773 | _ | _ | |a 10.1038/s41467-018-05769-2 |g Vol. 9, no. 1, p. 3559 |0 PERI:(DE-600)2553671-0 |n 1 |p 3559 |t Nature Communications |v 9 |y 2018 |x 2041-1723 |
| 856 | 4 | _ | |y OpenAccess |u https://juser.fz-juelich.de/record/859974/files/s41467-018-05769-2.pdf |
| 856 | 4 | _ | |y OpenAccess |x pdfa |u https://juser.fz-juelich.de/record/859974/files/s41467-018-05769-2.pdf?subformat=pdfa |
| 909 | C | O | |o oai:juser.fz-juelich.de:859974 |p openaire |p open_access |p driver |p VDB:MLZ |p VDB |p dnbdelivery |
| 910 | 1 | _ | |a Forschungszentrum Jülich |0 I:(DE-588b)5008462-8 |k FZJ |b 5 |6 P:(DE-Juel1)138266 |
| 910 | 1 | _ | |a Heinz Maier-Leibnitz Zentrum |0 I:(DE-588b)4597118-3 |k MLZ |b 7 |6 0000-0002-1477-5590 |
| 913 | 1 | _ | |a DE-HGF |9 G:(DE-HGF)POF3-6G15 |x 0 |4 G:(DE-HGF)POF |v FRM II / MLZ |1 G:(DE-HGF)POF3-6G0 |0 G:(DE-HGF)POF3-6G15 |3 G:(DE-HGF)POF3 |2 G:(DE-HGF)POF3-600 |b Forschungsbereich Materie |l Großgeräte: Materie |
| 913 | 1 | _ | |a DE-HGF |b Forschungsbereich Materie |l Von Materie zu Materialien und Leben |1 G:(DE-HGF)POF3-620 |0 G:(DE-HGF)POF3-623 |2 G:(DE-HGF)POF3-600 |v Facility topic: Neutrons for Research on Condensed Matter |9 G:(DE-HGF)POF3-6G4 |x 1 |4 G:(DE-HGF)POF |3 G:(DE-HGF)POF3 |
| 913 | 1 | _ | |a DE-HGF |b Forschungsbereich Materie |l Von Materie zu Materialien und Leben |1 G:(DE-HGF)POF3-620 |0 G:(DE-HGF)POF3-621 |2 G:(DE-HGF)POF3-600 |v In-house research on the structure, dynamics and function of matter |9 G:(DE-HGF)POF3-6215 |x 2 |4 G:(DE-HGF)POF |3 G:(DE-HGF)POF3 |
| 914 | 1 | _ | |y 2018 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |
| 915 | _ | _ | |a Creative Commons Attribution CC BY 4.0 |0 LIC:(DE-HGF)CCBY4 |2 HGFVOC |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1040 |2 StatID |b Zoological Record |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b NAT COMMUN : 2017 |
| 915 | _ | _ | |a IF >= 10 |0 StatID:(DE-HGF)9910 |2 StatID |b NAT COMMUN : 2017 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0501 |2 StatID |b DOAJ Seal |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0500 |2 StatID |b DOAJ |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0110 |2 StatID |b Science Citation Index |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0111 |2 StatID |b Science Citation Index Expanded |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1150 |2 StatID |b Current Contents - Physical, Chemical and Earth Sciences |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |
| 915 | _ | _ | |a OpenAccess |0 StatID:(DE-HGF)0510 |2 StatID |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b DOAJ : Blind peer review |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1060 |2 StatID |b Current Contents - Agriculture, Biology and Environmental Sciences |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0310 |2 StatID |b NCBI Molecular Biology Database |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0320 |2 StatID |b PubMed Central |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |
| 920 | _ | _ | |l yes |
| 920 | 1 | _ | |0 I:(DE-Juel1)JCNS-FRM-II-20110218 |k JCNS-FRM-II |l JCNS-FRM-II |x 0 |
| 920 | 1 | _ | |0 I:(DE-Juel1)JCNS-1-20110106 |k Neutronenstreuung ; JCNS-1 |l Neutronenstreuung |x 1 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a UNRESTRICTED |
| 980 | _ | _ | |a I:(DE-Juel1)JCNS-FRM-II-20110218 |
| 980 | _ | _ | |a I:(DE-Juel1)JCNS-1-20110106 |
| 980 | 1 | _ | |a FullTexts |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|