Rational design of allosterically regulated toehold mediated strand displacement circuit for sensitive and on-site detection of small molecule metabolites

The Analyst ◽  
2021 ◽  
Author(s):  
Haosi Lin ◽  
Alan F. Rodríguez-Serrano ◽  
I-Ming Hsing
Keyword(s):  
Transcription Factor ◽  
Small Molecule ◽  
Health Monitoring ◽  
Rational Design ◽  
Rapid Diagnosis ◽  
Strand Displacement ◽  
Small Molecule Detection

Development of small molecule biosensor enables rapid and de-centralized small molecule detection that meets the demand of routine health monitoring and rapid diagnosis. Among them, allosteric transcription factor (aTF)-based biosensors...

Development of small molecule biosensors by coupling the recognition of the bacterial allosteric transcription factor with isothermal strand displacement amplification

2018 ◽  
Vol 54 (38) ◽  
pp. 4774-4777 ◽  
Author(s):  
Yongpeng Yao ◽  
Shanshan Li ◽  
Jiaqian Cao ◽  
Weiwei Liu ◽  
Keqiang Fan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Small Molecule ◽  
Strand Displacement ◽  
Strand Displacement Amplification

We demonstrate a novel small molecule biosensing strategy by coupling the recognition of aTF with SDA reaction in vitro.

Inhibition of NGLY1 inactivates the transcription factor Nrf1 and potentiates proteasome inhibitor cytotoxicity

2017 ◽  
Author(s):  
Carolyn Bertozzi ◽  
Fred Tomlin ◽  
Ulla Gerling-Driessen ◽  
Yi-Chang Liu ◽  
Ryan Flynn ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Small Molecule ◽  
Proteasome Inhibitor ◽  
Activation Mechanism ◽  
Cancer Drugs ◽  
Small Molecule Library ◽  
Library Screen ◽  
In Cells

We discovered that the proteostasis modulating transcription factor Nrf1 requires cytosolic de-N-glycosylation by the N-glycanase NGly1 as part of its activation mechanism. Through a covalent small molecule library screen, we discovered an inhibitor of NGly1 that blocks Nrf1 activation in cells and potentiates the activity of proteasome inhibitor cancer drugs. The requirement of NGly1 for Nrf1 activity likely underlies several pathologies associated with a rare hereditary deficiency in NGly1.

scholarly journals Correction: Rational design of a stapled JAZ9 peptide inhibiting protein–protein interaction of a plant transcription factor

2021 ◽  
Author(s):  
Kaho Suzuki ◽  
Yousuke Takaoka ◽  
Minoru Ueda
Keyword(s):  
Transcription Factor ◽  
Protein Interaction ◽  
Rational Design ◽  
Protein Protein Interaction ◽  
Inhibiting Protein

Correction for ‘Rational design of a stapled JAZ9 peptide inhibiting protein–protein interaction of a plant transcription factor’ by Kaho Suzuki et al., RSC Chem. Biol., 2021, DOI: 10.1039/d0cb00204f.

scholarly journals Rational design of a stapled JAZ9 peptide inhibiting protein–protein interaction of a plant transcription factor

2021 ◽  
Author(s):  
Kaho Suzuki ◽  
Yousuke Takaoka ◽  
Minoru Ueda
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Protein Interaction ◽  
Rational Design ◽  
Master Regulators ◽  
Jasmonate Signaling ◽  
Protein Protein Interaction ◽  
Inhibiting Protein

A rationally designed stapled JAZ peptide selectively inhibited MYCs, master-regulators of the jasmonate signaling in Arabidopsis thaliana. It is proposed as a novel chemical tool for the analysis of MYC related jasmonate signaling.

scholarly journals RCO-3 and COL-26 form an external-to-internal module that regulates the dual-affinity glucose transport system in Neurospora crassa

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jinyang Li ◽  
Qian Liu ◽  
Jingen Li ◽  
Liangcai Lin ◽  
Xiaolin Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neurospora Crassa ◽  
Glucose Transport ◽  
Transport System ◽  
Rational Design ◽  
Glucose Sensor ◽  
Glucose Transporters ◽  
Glucose Fluctuation ◽  
High Affinity ◽  
Glucose Transport System

Abstract Background Low- and high-affinity glucose transport system is a conserved strategy of microorganism to cope with environmental glucose fluctuation for their growth and competitiveness. In Neurospora crassa, the dual-affinity glucose transport system consists of a low-affinity glucose transporter GLT-1 and two high-affinity glucose transporters HGT-1/HGT-2, which play diverse roles in glucose transport, carbon metabolism, and cellulase expression regulation. However, the regulation of this dual-transporter system in response to environmental glucose fluctuation is not yet clear. Results In this study, we report that a regulation module consisting of a downstream transcription factor COL-26 and an upstream non-transporting glucose sensor RCO-3 regulates the dual-affinity glucose transport system in N. crassa. COL-26 directly binds to the promoter regions of glt-1, hgt-1, and hgt-2, whereas RCO-3 is an upstream factor of the module whose deletion mutant resembles the Δcol-26 mutant phenotypically. Transcriptional profiling analysis revealed that Δcol-26 and Δrco-3 mutants had similar transcriptional profiles, and both mutants had impaired response to a glucose gradient. We also showed that the AMP-activated protein kinase (AMPK) complex is involved in regulation of the glucose transporters. AMPK is required for repression of glt-1 expression in starvation conditions by inhibiting the activity of RCO-3. Conclusions RCO-3 and COL-26 form an external-to-internal module that regulates the glucose dual-affinity transport system. Transcription factor COL-26 was identified as the key regulator. AMPK was also involved in the regulation of the dual-transporter system. Our findings provide novel insight into the molecular basis of glucose uptake and signaling in filamentous fungi, which may aid in the rational design of fungal strains for industrial purposes.

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