PMID- 34956689
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211228
IS  - 2155-5435 (Print)
IS  - 2155-5435 (Electronic)
VI  - 11
IP  - 24
DP  - 2021 Dec 17
TI  - Chemical Mapping Exposes the Importance of Active Site Interactions in Governing 
      the Temperature Dependence of Enzyme Turnover.
PG  - 14854-14863
LID - 10.1021/acscatal.1c04679 [doi]
AB  - Uncovering the role of global protein dynamics in enzyme turnover is needed to 
      fully understand enzyme catalysis. Recently, we have demonstrated that the heat 
      capacity of catalysis, DeltaC (P) (double dagger), can reveal links between the protein free 
      energy landscape, global protein dynamics, and enzyme turnover, suggesting that 
      subtle changes in molecular interactions at the active site can affect long-range 
      protein dynamics and link to enzyme temperature activity. Here, we use a model 
      promiscuous enzyme (glucose dehydrogenase from Sulfolobus solfataricus) to 
      chemically map how individual substrate interactions affect the temperature 
      dependence of enzyme activity and the network of motions throughout the protein. 
      Utilizing a combination of kinetics, red edge excitation shift (REES) 
      spectroscopy, and computational simulation, we explore the complex relationship 
      between enzyme-substrate interactions and the global dynamics of the protein. We 
      find that changes in DeltaC (P) (double dagger) and protein dynamics can be mapped to specific 
      substrate-enzyme interactions. Our study reveals how subtle changes in substrate 
      binding affect global changes in motion and flexibility extending throughout the 
      protein.
CI  - (c) 2021 The Authors. Published by American Chemical Society.
FAU - Winter, Samuel D
AU  - Winter SD
AD  - Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, U.K.
FAU - Jones, Hannah B L
AU  - Jones HBL
AD  - Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, U.K.
FAU - Rasadean, Dora M
AU  - Rasadean DM
AD  - Department of Chemistry, University of Bath, Bath BA2 7AY, U.K.
FAU - Crean, Rory M
AU  - Crean RM
AD  - Science for Life Laboratory, Department of Chemistry - BMC, Uppsala University, 
      Uppsala 752 37, Sweden.
FAU - Danson, Michael J
AU  - Danson MJ
AD  - Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, U.K.
FAU - Pantos, G Dan
AU  - Pantos GD
AD  - Department of Chemistry, University of Bath, Bath BA2 7AY, U.K.
FAU - Katona, Gergely
AU  - Katona G
AD  - Department of Chemistry and Biology, University of Gothenburg, Goteborg 412 96, 
      Sweden.
FAU - Prentice, Erica
AU  - Prentice E
AUID- ORCID: 0000-0001-7417-7296
AD  - School of Science, University of Waikato, Hamilton 3216, New Zealand.
FAU - Arcus, Vickery L
AU  - Arcus VL
AD  - School of Science, University of Waikato, Hamilton 3216, New Zealand.
FAU - van der Kamp, Marc W
AU  - van der Kamp MW
AUID- ORCID: 0000-0002-8060-3359
AD  - Department of Biochemistry, University of Bristol, Bristol BS8 1TD, U.K.
FAU - Pudney, Christopher R
AU  - Pudney CR
AUID- ORCID: 0000-0001-6211-0086
AD  - Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, U.K.
LA  - eng
PT  - Journal Article
DEP - 20211129
PL  - United States
TA  - ACS Catal
JT  - ACS catalysis
JID - 101562209
PMC - PMC8689651
COIS- The authors declare no competing financial interest.
EDAT- 2021/12/28 06:00
MHDA- 2021/12/28 06:01
PMCR- 2021/12/21
CRDT- 2021/12/27 06:30
PHST- 2021/10/11 00:00 [received]
PHST- 2021/11/16 00:00 [revised]
PHST- 2021/12/27 06:30 [entrez]
PHST- 2021/12/28 06:00 [pubmed]
PHST- 2021/12/28 06:01 [medline]
PHST- 2021/12/21 00:00 [pmc-release]
AID - 10.1021/acscatal.1c04679 [doi]
PST - ppublish
SO  - ACS Catal. 2021 Dec 17;11(24):14854-14863. doi: 10.1021/acscatal.1c04679. Epub 
      2021 Nov 29.