Elucidation and control of low and high active populations of alkaline phosphatase molecules for quantitative digital bioassay.


Journal

Protein science : a publication of the Protein Society
ISSN: 1469-896X
Titre abrégé: Protein Sci
Pays: United States
ID NLM: 9211750

Informations de publication

Date de publication:
08 2021
Historique:
revised: 27 04 2021
received: 04 02 2021
accepted: 02 05 2021
pubmed: 7 5 2021
medline: 1 2 2022
entrez: 6 5 2021
Statut: ppublish

Résumé

Alkaline phosphatase (ALP), a homo-dimeric enzyme has been widely used in various bioassays as disease markers and enzyme probes. Recent advancements of digital bioassay revolutionized ALP-based diagnostic assays as seen in rapid growth of digital ELISA and the emerging multiplex profiling of single-molecule ALP isomers. However, the intrinsic heterogeneity found among ALP molecules hampers the ALP-based quantitative digital bioassays. This study aims quantitative analysis of single-molecule activities of ALP from Escherichia coli and reveals the static heterogeneity in catalytic activity of ALP with two distinct populations: half-active and fully-active portions. Digital assays with serial buffer exchange uncovered single-molecule Michaelis-Menten kinetics of ALP; half-active molecules have halved values of the catalytic turnover rate, k

Identifiants

pubmed: 33955095
doi: 10.1002/pro.4102
pmc: PMC8284569
doi:

Substances chimiques

Escherichia coli Proteins 0
Alkaline Phosphatase EC 3.1.3.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1628-1639

Informations de copyright

© 2021 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.

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Auteurs

Hiroshi Ueno (H)

Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.

Makoto Kato (M)

Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.

Yoshihiro Minagawa (Y)

Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.

Yushi Hirose (Y)

Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.

Hiroyuki Noji (H)

Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.

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Classifications MeSH