Home > Publications database > Loop Motion in Triosephosphate Isomerase Is Not a Simple Open and Shut Case > print

001     858904
005     20210130000131.0
024 7 _ |a 10.1021/jacs.8b09378
|2 doi
024 7 _ |a 0002-7863
|2 ISSN
024 7 _ |a 1520-5126
|2 ISSN
024 7 _ |a 1943-2984
|2 ISSN
024 7 _ |a 2128/21055
|2 Handle
024 7 _ |a pmid:30362343
|2 pmid
024 7 _ |a WOS:000451496800048
|2 WOS
024 7 _ |a altmetric:50323813
|2 altmetric
037 _ _ |a FZJ-2018-07740
082 _ _ |a 540
100 1 _ |a Liao, Qinghua
|0 P:(DE-HGF)0
|b 0
245 _ _ |a Loop Motion in Triosephosphate Isomerase Is Not a Simple Open and Shut Case
260 _ _ |a Washington, DC
|c 2018
|b American Chemical Society
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 1546496224_1134
|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 Conformational changes are crucial for the catalytic action of many enzymes. A prototypical and well-studied example is loop opening and closure in triosephosphate isomerase (TIM), which is thought to determine the rate of catalytic turnover in many circumstances. Specifically, TIM loop 6 “grips” the phosphodianion of the substrate and, together with a change in loop 7, sets up the TIM active site for efficient catalysis. Crystal structures of TIM typically show an open or a closed conformation of loop 6, with the tip of the loop moving ∼7 Å between conformations. Many studies have interpreted this motion as a two-state, rigid-body transition. Here, we use extensive molecular dynamics simulations, with both conventional and enhanced sampling techniques, to analyze loop motion in apo and substrate-bound TIM in detail, using five crystal structures of the dimeric TIM from Saccharomyces cerevisiae. We find that loop 6 is highly flexible and samples multiple conformational states. Empirical valence bond simulations of the first reaction step show that slight displacements away from the fully closed-loop conformation can be sufficient to abolish most of the catalytic activity; full closure is required for efficient reaction. The conformational change of the loops in TIM is thus not a simple “open and shut” case and is crucial for its catalytic action. Our detailed analysis of loop motion in a highly efficient enzyme highlights the complexity of loop conformational changes and their role in biological catalysis.
536 _ _ |a 551 - Functional Macromolecules and Complexes (POF3-551)
|0 G:(DE-HGF)POF3-551
|c POF3-551
|f POF III
|x 0
588 _ _ |a Dataset connected to CrossRef
700 1 _ |a Kulkarni, Yashraj
|0 P:(DE-HGF)0
|b 1
700 1 _ |a Sengupta, Ushnish
|0 P:(DE-HGF)0
|b 2
700 1 _ |a Petrović, Dušan
|0 P:(DE-Juel1)165744
|b 3
700 1 _ |a Mulholland, Adrian J.
|0 0000-0003-1015-4567
|b 4
700 1 _ |a van der Kamp, Marc W.
|0 0000-0002-8060-3359
|b 5
700 1 _ |a Strodel, Birgit
|0 P:(DE-Juel1)132024
|b 6
700 1 _ |a Kamerlin, Shina Caroline Lynn
|0 0000-0002-3190-1173
|b 7
|e Corresponding author
773 _ _ |a 10.1021/jacs.8b09378
|g Vol. 140, no. 46, p. 15889 - 15903
|0 PERI:(DE-600)1472210-0
|n 46
|p 15889 - 15903
|t Journal of the American Chemical Society
|v 140
|y 2018
|x 1520-5126
856 4 _ |y OpenAccess
|u https://juser.fz-juelich.de/record/858904/files/Loop%20Motion%20in%20Triosephosphate%20Isomerase%20Is%20Not%20a%20Simple%20Open%20and%20Shut%20Case.pdf
856 4 _ |y OpenAccess
|x pdfa
|u https://juser.fz-juelich.de/record/858904/files/Loop%20Motion%20in%20Triosephosphate%20Isomerase%20Is%20Not%20a%20Simple%20Open%20and%20Shut%20Case.pdf?subformat=pdfa
909 C O |o oai:juser.fz-juelich.de:858904
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 6
|6 P:(DE-Juel1)132024
913 1 _ |a DE-HGF
|b Key Technologies
|l BioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences
|1 G:(DE-HGF)POF3-550
|0 G:(DE-HGF)POF3-551
|2 G:(DE-HGF)POF3-500
|v Functional Macromolecules and Complexes
|x 0
|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 DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
915 _ _ |a Free to read
|0 LIC:(DE-HGF)PublisherOA
|2 HGFVOC
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b J AM CHEM SOC : 2017
915 _ _ |a IF >= 10
|0 StatID:(DE-HGF)9910
|2 StatID
|b J AM CHEM SOC : 2017
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
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 OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
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)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 Nationallizenz
|0 StatID:(DE-HGF)0420
|2 StatID
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)ICS-6-20110106
|k ICS-6
|l Strukturbiochemie
|x 0
980 1 _ |a FullTexts
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-Juel1)ICS-6-20110106
981 _ _ |a I:(DE-Juel1)IBI-7-20200312

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21