PMID- 34516596
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20210927
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 23
IP  - 36
DP  - 2021 Sep 22
TI  - Enzyme aggregation and fragmentation induced by catalysis relevant species.
PG  - 20709-20717
LID - 10.1039/d1cp02966e [doi]
AB  - It is usually assumed that enzymes retain their native structure during 
      catalysis. However, the aggregation and fragmentation of proteins can be 
      difficult to detect and sometimes conclusions are drawn based on the assumption 
      that the protein is in its native form. We have examined three model enzymes, 
      alkaline phosphatase (AkP), hexokinase (HK) and glucose oxidase (GOx). We find 
      that these enzymes aggregate or fragment after addition of chemical species 
      directly related to their catalysis. We used several independent techniques to 
      study this behavior. Specifically, we found that glucose oxidase and hexokinase 
      fragment in the presence of D-glucose but not L-glucose, while hexokinase 
      aggregates in the presence of Mg(2+) ion and either ATP or ADP at low pH. 
      Alkaline phosphatase aggregates in the presence of Zn(2+) ion and inorganic 
      phosphate. The aggregation of hexokinase and alkaline phosphatase does not appear 
      to attenuate their catalytic activity. Our study indicates that specific 
      multimeric structures of native enzymes may not be retained during catalysis and 
      suggests pathways for different enzymes to associate or separate over the course 
      of substrate turnover.
FAU - Gentile, Kayla
AU  - Gentile K
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA. asen@psu.edu.
FAU - Bhide, Ashlesha
AU  - Bhide A
AUID- ORCID: 0000-0002-3082-9819
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA. asen@psu.edu.
FAU - Kauffman, Joshua
AU  - Kauffman J
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA. asen@psu.edu.
FAU - Ghosh, Subhadip
AU  - Ghosh S
AUID- ORCID: 0000-0001-6880-7052
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA. asen@psu.edu.
FAU - Maiti, Subhabrata
AU  - Maiti S
AUID- ORCID: 0000-0002-2554-0762
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA. asen@psu.edu.
FAU - Adair, James
AU  - Adair J
AD  - Department of Materials Science and Engineering, The Pennsylvania State 
      University, University Park, PA 16802, USA.
FAU - Lee, Tae-Hee
AU  - Lee TH
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA. asen@psu.edu.
FAU - Sen, Ayusman
AU  - Sen A
AUID- ORCID: 0000-0002-0556-9509
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA. asen@psu.edu.
LA  - eng
PT  - Journal Article
DEP - 20210922
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - 0 (Protein Aggregates)
RN  - EC 1.1.3.4 (Glucose Oxidase)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/*chemistry/metabolism
MH  - Biocatalysis
MH  - Glucose Oxidase/*chemistry/metabolism
MH  - Hexokinase/*chemistry/metabolism
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Protein Aggregates
EDAT- 2021/09/14 06:00
MHDA- 2021/09/28 06:00
CRDT- 2021/09/13 17:29
PHST- 2021/09/14 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2021/09/13 17:29 [entrez]
AID - 10.1039/d1cp02966e [doi]
PST - epublish
SO  - Phys Chem Chem Phys. 2021 Sep 22;23(36):20709-20717. doi: 10.1039/d1cp02966e.