000860022 001__ 860022
000860022 005__ 20240619092119.0
000860022 0247_ $$2doi$$a10.1021/acs.bioconjchem.8b00203
000860022 0247_ $$2ISSN$$a1043-1802
000860022 0247_ $$2ISSN$$a1520-4812
000860022 0247_ $$2pmid$$apmid:29847099
000860022 0247_ $$2WOS$$aWOS:000436211700019
000860022 037__ $$aFZJ-2019-00819
000860022 082__ $$a540
000860022 1001_ $$0P:(DE-Juel1)166487$$aCiepluch, Karol$$b0$$eCorresponding author
000860022 245__ $$aInfluence of PEGylation on Domain Dynamics of Phosphoglycerate Kinase: PEG Acts Like Entropic Spring for the Protein
000860022 260__ $$aColumbus, Ohio$$bAmerican Chemical Society$$c2018
000860022 3367_ $$2DRIVER$$aarticle
000860022 3367_ $$2DataCite$$aOutput Types/Journal article
000860022 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1553871565_25990
000860022 3367_ $$2BibTeX$$aARTICLE
000860022 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000860022 3367_ $$00$$2EndNote$$aJournal Article
000860022 520__ $$aProtein–polymer conjugation is a widely used technique to develop protein therapeutics with improved pharmacokinetic properties as prolonged half-life, higher stability, water solubility, lower immunogenicity, and antigenicity. Combining biochemical methods, small angle scattering (SAXS/SANS), and neutron spin–echo spectroscopy, here we examine the impact of PEGylation (i.e., the covalent conjugation with poly(ethylene glycol) or PEG) on structure and internal domain dynamics of phosphoglycerate kinase (PGK) to elucidate the reason for reduced activity that is connected to PEGylation. PGK is a protein with a hinge motion between the two main domains that is directly related to function. We find that secondary structure and ligand access to the binding sites are not affected. The ligand induced cleft closing is unchanged. We observe an additional internal motion between covalent bonded PEG and the protein compatible with Brownian motion of PGK in a harmonic potential. Entropic interaction with the full PEG chain leads to a force constant of about 8 pN/nm independent of PEG chain length. This additional force preserves protein structure and has negligible effects on the functional domain dynamics of the protein. PEGylation seems to reduce activity just by acting as a local crowder for the ligands. The newly identified interaction mechanism might open possibilities to improve rational design of protein–polymer conjugates.
000860022 536__ $$0G:(DE-HGF)POF3-551$$a551 - Functional Macromolecules and Complexes (POF3-551)$$cPOF3-551$$fPOF III$$x0
000860022 536__ $$0G:(DE-HGF)POF3-6G4$$a6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)$$cPOF3-623$$fPOF III$$x1
000860022 536__ $$0G:(DE-HGF)POF3-6215$$a6215 - Soft Matter, Health and Life Sciences (POF3-621)$$cPOF3-621$$fPOF III$$x2
000860022 588__ $$aDataset connected to CrossRef
000860022 65027 $$0V:(DE-MLZ)SciArea-160$$2V:(DE-HGF)$$aBiology$$x0
000860022 65027 $$0V:(DE-MLZ)SciArea-110$$2V:(DE-HGF)$$aChemistry$$x1
000860022 65017 $$0V:(DE-MLZ)GC-130-2016$$2V:(DE-HGF)$$aHealth and Life$$x0
000860022 693__ $$0EXP:(DE-MLZ)KWS2-20140101$$1EXP:(DE-MLZ)FRMII-20140101$$5EXP:(DE-MLZ)KWS2-20140101$$6EXP:(DE-MLZ)NL3ao-20140101$$aForschungs-Neutronenquelle Heinz Maier-Leibnitz $$eKWS-2: Small angle scattering diffractometer$$fNL3ao$$x0
000860022 7001_ $$0P:(DE-Juel1)130905$$aRadulescu, Aurel$$b1
000860022 7001_ $$0P:(DE-HGF)0$$aHoffmann, Ingo$$b2
000860022 7001_ $$0P:(DE-Juel1)166570$$aRaba, Andreas$$b3
000860022 7001_ $$0P:(DE-Juel1)130501$$aAllgaier, Jürgen$$b4
000860022 7001_ $$0P:(DE-Juel1)130917$$aRichter, Dieter$$b5
000860022 7001_ $$0P:(DE-Juel1)130542$$aBiehl, Ralf$$b6$$eCorresponding author
000860022 773__ $$0PERI:(DE-600)1500067-9$$a10.1021/acs.bioconjchem.8b00203$$gVol. 29, no. 6, p. 1950 - 1960$$n6$$p1950 - 1960$$tBioconjugate chemistry$$v29$$x1520-4812$$y2018
000860022 8564_ $$uhttps://juser.fz-juelich.de/record/860022/files/acs.bioconjchem.8b00203.pdf$$yRestricted
000860022 8564_ $$uhttps://juser.fz-juelich.de/record/860022/files/acs.bioconjchem.8b00203.pdf?subformat=pdfa$$xpdfa$$yRestricted
000860022 909CO $$ooai:juser.fz-juelich.de:860022$$pVDB$$pVDB:MLZ
000860022 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)130905$$aForschungszentrum Jülich$$b1$$kFZJ
000860022 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)130501$$aForschungszentrum Jülich$$b4$$kFZJ
000860022 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)130917$$aForschungszentrum Jülich$$b5$$kFZJ
000860022 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)130542$$aForschungszentrum Jülich$$b6$$kFZJ
000860022 9131_ $$0G:(DE-HGF)POF3-551$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vFunctional Macromolecules and Complexes$$x0
000860022 9131_ $$0G:(DE-HGF)POF3-623$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF3-6G4$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vFacility topic: Neutrons for Research on Condensed Matter$$x1
000860022 9131_ $$0G:(DE-HGF)POF3-621$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF3-6215$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vIn-house research on the structure, dynamics and function of matter$$x2
000860022 9141_ $$y2018
000860022 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000860022 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBIOCONJUGATE CHEM : 2017
000860022 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000860022 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000860022 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000860022 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000860022 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000860022 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000860022 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000860022 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000860022 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000860022 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000860022 9201_ $$0I:(DE-Juel1)JCNS-1-20110106$$kNeutronenstreuung ; JCNS-1$$lNeutronenstreuung $$x0
000860022 9201_ $$0I:(DE-Juel1)ICS-1-20110106$$kICS-1$$lNeutronenstreuung $$x1
000860022 9201_ $$0I:(DE-Juel1)JCNS-FRM-II-20110218$$kJCNS-FRM-II$$lJCNS-FRM-II$$x2
000860022 980__ $$ajournal
000860022 980__ $$aVDB
000860022 980__ $$aI:(DE-Juel1)JCNS-1-20110106
000860022 980__ $$aI:(DE-Juel1)ICS-1-20110106
000860022 980__ $$aI:(DE-Juel1)JCNS-FRM-II-20110218
000860022 980__ $$aUNRESTRICTED
000860022 981__ $$aI:(DE-Juel1)IBI-8-20200312
000860022 981__ $$aI:(DE-Juel1)JCNS-1-20110106