000857897 001__ 857897
000857897 005__ 20210129235752.0
000857897 0247_ $$2doi$$a10.1039/C7CP08470F
000857897 0247_ $$2ISSN$$a1463-9076
000857897 0247_ $$2ISSN$$a1463-9084
000857897 0247_ $$2pmid$$apmid:29578220
000857897 0247_ $$2WOS$$aWOS:000429205700059
000857897 037__ $$aFZJ-2018-06851
000857897 082__ $$a540
000857897 1001_ $$0P:(DE-Juel1)161153$$aZhao, Jing$$b0
000857897 245__ $$aUnraveling the effects of amino acid substitutions enhancing lipase resistance to an ionic liquid: a molecular dynamics study
000857897 260__ $$aCambridge$$bRSC Publ.66479$$c2018
000857897 3367_ $$2DRIVER$$aarticle
000857897 3367_ $$2DataCite$$aOutput Types/Journal article
000857897 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1552634249_8447
000857897 3367_ $$2BibTeX$$aARTICLE
000857897 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000857897 3367_ $$00$$2EndNote$$aJournal Article
000857897 520__ $$aUnderstanding of the structural and dynamic properties of enzymes in non-aqueous media (e.g., ionic liquids, ILs) is highly attractive for protein engineers and synthetic biochemists. Despite a growing number of molecular dynamics (MD) simulation studies on the influence of different ILs on wild-type enzymes, the effects of various amino acid substitutions on the stability and activity of enzymes in ILs remain to be unraveled at the molecular level. Herein, we selected fifty previously reported Bacillus subtilis lipase A (BSLA) variants with increased resistance towards an IL (15 vol% 1-butyl-3-methylimidazolium trifluoromethanesulfonate; [Bmim][TfO]), and also ten non-resistant BSLA variants for a MD simulation study to identify the underlying molecular principles. Some important properties differentiating resistant and non-resistant BSLA variants from wild-type were elucidated. Results show that, in 15 vol% [Bmim][TfO] aqueous solution, 40% and 60% of non-resistant variants have lower and equal probabilities to form a catalytically important hydrogen bond between S77 and H156 compared to wild-type, whereas 36% and 56% of resistant variants show increased and equal probabilities, respectively. Introducing positively charged amino acids close to the substrate-binding cleft for instance I12R is beneficial for the BSLA resistance towards 15 vol% [Bmim][TfO], likely due to the reduced probability of [Bmim]+ cations clustering near the cleft. In contrast, substitution with a large hydrophobic residue like I12F can block the cleft through hydrophobic interaction with a neighboring nonpolar loop 134–137 or/and an attractive π–π interaction with [Bmim]+ cations. In addition, the resistant variants having polar substitutions on the surface show higher ability to stabilize the surface water molecule network in comparison to non-resistant variants. This study can guide experimentalists to rationally design promising IL–resistant enzymes, and contribute to a deeper understanding of protein–IL interactions at the molecular level.
000857897 536__ $$0G:(DE-HGF)POF3-581$$a581 - Biotechnology (POF3-581)$$cPOF3-581$$fPOF III$$x0
000857897 536__ $$0G:(DE-Juel1)jara0169_20170501$$aTowards Discovery of Molecular Determinants Underlying Organic Solvent Resistance of Enzymes: Large- (jara0169_20170501)$$cjara0169_20170501$$fTowards Discovery of Molecular Determinants Underlying Organic Solvent Resistance of Enzymes: Large-$$x1
000857897 588__ $$aDataset connected to CrossRef
000857897 7001_ $$0P:(DE-HGF)0$$aFrauenkron-Machedjou, Victorine Josiane$$b1
000857897 7001_ $$0P:(DE-Juel1)143642$$aFulton, Alexander$$b2
000857897 7001_ $$0P:(DE-HGF)0$$aZhu, Leilei$$b3
000857897 7001_ $$0P:(DE-HGF)0$$aDavari, Mehdi D.$$b4
000857897 7001_ $$0P:(DE-Juel1)131457$$aJaeger, Karl-Erich$$b5
000857897 7001_ $$00000-0003-4026-701X$$aSchwaneberg, Ulrich$$b6
000857897 7001_ $$0P:(DE-HGF)0$$aBocola, Marco$$b7$$eCorresponding author
000857897 773__ $$0PERI:(DE-600)1476244-4$$a10.1039/C7CP08470F$$gVol. 20, no. 14, p. 9600 - 9609$$n14$$p9600 - 9609$$tPhysical chemistry, chemical physics$$v20$$x1463-9084$$y2018
000857897 8564_ $$uhttps://juser.fz-juelich.de/record/857897/files/c7cp08470f.pdf$$yRestricted
000857897 8564_ $$uhttps://juser.fz-juelich.de/record/857897/files/c7cp08470f.pdf?subformat=pdfa$$xpdfa$$yRestricted
000857897 909CO $$ooai:juser.fz-juelich.de:857897$$pVDB
000857897 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131457$$aForschungszentrum Jülich$$b5$$kFZJ
000857897 9131_ $$0G:(DE-HGF)POF3-581$$1G:(DE-HGF)POF3-580$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lKey Technologies for the Bioeconomy$$vBiotechnology$$x0
000857897 9141_ $$y2018
000857897 915__ $$0StatID:(DE-HGF)0400$$2StatID$$aAllianz-Lizenz / DFG
000857897 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000857897 915__ $$0StatID:(DE-HGF)0430$$2StatID$$aNational-Konsortium
000857897 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bPHYS CHEM CHEM PHYS : 2017
000857897 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000857897 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000857897 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000857897 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000857897 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000857897 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000857897 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000857897 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences
000857897 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000857897 9201_ $$0I:(DE-Juel1)IMET-20090612$$kIMET$$lInstitut für Molekulare Enzymtechnologie (HHUD)$$x0
000857897 9201_ $$0I:(DE-82)080012_20140620$$kJARA-HPC$$lJARA - HPC$$x1
000857897 980__ $$ajournal
000857897 980__ $$aVDB
000857897 980__ $$aI:(DE-Juel1)IMET-20090612
000857897 980__ $$aI:(DE-82)080012_20140620
000857897 980__ $$aUNRESTRICTED