Compartmentalized cAMP Generation by Engineered Photoactivated Adenylyl Cyclases.

Abstract:

:Because small-molecule activators of adenylyl cyclases (AC) affect ACs cell-wide, it is challenging to explore the signaling consequences of AC activity emanating from specific intracellular compartments. We explored this issue using a series of engineered, optogenetic, spatially restricted, photoactivable adenylyl cyclases (PACs) positioned at the plasma membrane (PM), the outer mitochondrial membrane (OMM), and the nucleus (Nu). The biochemical consequences of brief photostimulation of PAC is primarily limited to the intracellular site occupied by the PAC. By contrast, sustained photostimulation results in distal cAMP signaling. Prolonged cAMP generation at the OMM profoundly stimulates nuclear protein kinase (PKA) activity. We have found that phosphodiesterases 3 (OMM and PM) and 4 (PM) modulate proximal (local) cAMP-triggered activity, whereas phosphodiesterase 4 regulates distal cAMP activity as well as the migration of PKA's catalytic subunit into the nucleus.

journal_name

Cell Chem Biol

journal_title

Cell chemical biology

authors

O'Banion CP,Vickerman BM,Haar L,Lawrence DS

doi

10.1016/j.chembiol.2019.07.004

subject

Has Abstract

pub_date

2019-10-17 00:00:00

pages

1393-1406.e7

issue

10

eissn

2451-9456

issn

2451-9448

pii

S2451-9456(19)30216-8

journal_volume

26

pub_type

杂志文章
  • A Ratiometric Sensor for Imaging Insulin Secretion in Single β Cells.

    abstract::Despite the urgent need for assays to visualize insulin secretion there is to date no reliable method available for measuring insulin release from single cells. To address this need, we developed a genetically encoded reporter termed RINS1 based on proinsulin superfolder GFP (sfGFP) and mCherry fusions for monitoring ...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2017.03.001

    authors: Schifferer M,Yushchenko DA,Stein F,Bolbat A,Schultz C

    更新日期:2017-04-20 00:00:00

  • Epiblastin A Induces Reprogramming of Epiblast Stem Cells Into Embryonic Stem Cells by Inhibition of Casein Kinase 1.

    abstract::The discovery of novel small molecules that induce stem cell reprogramming and give efficient access to pluripotent stem cells is of major importance for potential therapeutic applications and may reveal novel insights into the factors controlling pluripotency. Chemical reprogramming of mouse epiblast stem cells (EpiS...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2016.02.015

    authors: Ursu A,Illich DJ,Takemoto Y,Porfetye AT,Zhang M,Brockmeyer A,Janning P,Watanabe N,Osada H,Vetter IR,Ziegler S,Schöler HR,Waldmann H

    更新日期:2016-04-21 00:00:00

  • Promises and Pitfalls of Metal Imaging in Biology.

    abstract::A picture may speak a thousand words, but if those words fail to form a coherent sentence there is little to be learned. As cutting-edge imaging technology now provides us the tools to decipher the multitude of roles played by metals and metalloids in molecular, cellular, and developmental biology, as well as health a...

    journal_title:Cell chemical biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.chembiol.2017.10.006

    authors: New EJ,Wimmer VC,Hare DJ

    更新日期:2018-01-18 00:00:00

  • Selective Inhibition of BFL1: It's All about Finding the Right Partner.

    abstract::In this issue of Cell Chemical Biology, Harvey et al. (2020) identify 4E14, a sulfhydryl-containing N-acetyltryptophan analog that selectively disrupts binding to the previously undruggable anti-apoptotic BCL2 paralog BFL1, and elucidate a BFL1 conformational change that facilitates 4E14 interaction. These results pro...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2020.05.014

    authors: Dai H,Meng XW,Kaufmann SH

    更新日期:2020-06-18 00:00:00

  • Investigation of Penicillin Binding Protein (PBP)-like Peptide Cyclase and Hydrolase in Surugamide Non-ribosomal Peptide Biosynthesis.

    abstract::Non-ribosomal peptides (NRPs) are biosynthesized on non-ribosomal peptides synthetase (NRPS) complexes, of which a C-terminal releasing domain commonly offloads the products. Interestingly, a dedicated releasing domain is absent in surugamides (SGM) NRPS, which directs the biosynthesis of cyclic octapeptides, SGM-A to...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2019.02.010

    authors: Zhou Y,Lin X,Xu C,Shen Y,Wang SP,Liao H,Li L,Deng H,Lin HW

    更新日期:2019-05-16 00:00:00

  • Small-Molecule TLR8 Antagonists via Structure-Based Rational Design.

    abstract::Rational design of drug-like small-molecule ligands based on structural information of proteins remains a significant challenge in chemical biology. In particular, designs targeting protein-protein interfaces have met little success given the dynamic nature of the protein surfaces. Herein, we utilized the structure of...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2018.07.004

    authors: Hu Z,Tanji H,Jiang S,Zhang S,Koo K,Chan J,Sakaniwa K,Ohto U,Candia A,Shimizu T,Yin H

    更新日期:2018-10-18 00:00:00

  • Catching Sirtuin-2 Intermediates One Structure at the Time.

    abstract::Sirtuins are a large enzyme family involved in installing and removing post-translational modifications involving lysine side chains. These enzymes have been of intense research interest and we now understand many details of their mechanism, although later steps of the deacetylase activity have remained a mystery. In ...

    journal_title:Cell chemical biology

    pub_type: 评论,杂志文章

    doi:10.1016/j.chembiol.2017.03.004

    authors: Lee S,Chen Z,Zhang G

    更新日期:2017-03-16 00:00:00

  • BMPing Up Healing Capacity with FKBP12 Ligand.

    abstract::While the wound healing property of the macrolide FK506 is well known, the underlying mechanism has been elusive. In this issue of Cell Chemical Biology, Peiffer et al. (2019) utilize FKBP12 ligand to demonstrate that wound healing effects of FK506 occur via activation of the BMP (bone morphogenic protein) signaling p...

    journal_title:Cell chemical biology

    pub_type: 评论,杂志文章

    doi:10.1016/j.chembiol.2019.05.001

    authors: Williams CH,Hong CC

    更新日期:2019-05-16 00:00:00

  • Privileged Electrophile Sensors: A Resource for Covalent Drug Development.

    abstract::This Perspective delineates how redox signaling affects the activity of specific enzyme isoforms and how this property may be harnessed for rational drug design. Covalent drugs have resurged in recent years and several reports have extolled the general virtues of developing irreversible inhibitors. Indeed, many modern...

    journal_title:Cell chemical biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.chembiol.2017.05.023

    authors: Long MJC,Aye Y

    更新日期:2017-07-20 00:00:00

  • Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets.

    abstract::Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a promising class of targeted cancer drugs, but their individual target profiles beyond the PARP family, which could result in differential clinical use or toxicity, are unknown. Using an unbiased, mass spectrometry-based chemical proteomics approach, we genera...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2016.10.011

    authors: Knezevic CE,Wright G,Rix LLR,Kim W,Kuenzi BM,Luo Y,Watters JM,Koomen JM,Haura EB,Monteiro AN,Radu C,Lawrence HR,Rix U

    更新日期:2016-12-22 00:00:00

  • Discovery of a Small Molecule Promoting Mouse and Human Osteoblast Differentiation via Activation of p38 MAPK-β.

    abstract::Disorders of bone healing and remodeling are indications with an unmet need for effective pharmacological modulators. We used a high-throughput screen to identify activators of the bone marker alkaline phosphatase (ALP), and discovered 6,8-dimethyl-3-(4-phenyl-1H-imidazol-5-yl)quinolin-2(1H)-one (DIPQUO). DIPQUO marke...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2019.03.009

    authors: Cook B,Rafiq R,Lee H,Banks KM,El-Debs M,Chiaravalli J,Glickman JF,Das BC,Chen S,Evans T

    更新日期:2019-07-18 00:00:00

  • Membrane-Active Rhamnolipids Overcome Aminoglycoside Resistance.

    abstract::In this issue of Cell Chemical Biology, Radlinski et al. (2019) identify Pseudomonas-derived rhamnolipids that potentiate aminoglycoside antibiotics in the eradication of antibiotic-tolerant bacterial phenotypes. Microbial physiological and mechanistic studies indicate that rhamnolipids permeabilize S. aureus membrane...

    journal_title:Cell chemical biology

    pub_type: 评论,杂志文章

    doi:10.1016/j.chembiol.2019.09.015

    authors: Yarlagadda V,Wright GD

    更新日期:2019-10-17 00:00:00

  • Targeted Degradation of a Hypoxia-Associated Non-coding RNA Enhances the Selectivity of a Small Molecule Interacting with RNA.

    abstract::Small-molecule targeted recruitment of nucleases to RNA is a powerful method to affect RNA biology. Inforna, a sequence-based design approach to target RNA, enables the design of small molecules that bind to and cleave RNA in a selective and substoichiometric manner. Here, we investigate the ability of RNA-targeted de...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2019.04.008

    authors: Costales MG,Suresh B,Vishnu K,Disney MD

    更新日期:2019-08-15 00:00:00

  • No Bones About It: Small Molecules for Bone Regeneration.

    abstract::In this issue of Cell Chemical Biology, Cook et al. (2019) report a new small-molecule activator that enhances osteogenesis and skeletal regeneration in developmental and adult animal models, respectively. This discovery has therapeutic potential for healing following traumatic bone injury, as well as bone remodeling ...

    journal_title:Cell chemical biology

    pub_type: 评论,杂志文章

    doi:10.1016/j.chembiol.2019.06.007

    authors: Chang JW,Moellering RE

    更新日期:2019-07-18 00:00:00

  • Discovery of an Inhibitor for Bacterial 3-Mercaptopyruvate Sulfurtransferase that Synergistically Controls Bacterial Survival.

    abstract::H2S-producing enzymes in bacteria have been shown to be closely engaged in the process of microbial survival and antibiotic resistance. However, no inhibitors have been discovered for these enzymes, e.g., 3-mercaptopyruvate sulfurtransferase (MST). In the present study, we identified several classes of inhibitors for ...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2020.10.012

    authors: Croppi G,Zhou Y,Yang R,Bian Y,Zhao M,Hu Y,Ruan BH,Yu J,Wu F

    更新日期:2020-12-17 00:00:00

  • Crystal Structure of a Group I Energy Coupling Factor Vitamin Transporter S Component in Complex with Its Cognate Substrate.

    abstract::Energy coupling factor (ECF) transporters are responsible for the uptake of essential scarce nutrients in prokaryotes. This ATP-binding cassette transporter family comprises two subgroups that share a common architecture forming a tripartite membrane protein complex consisting of a translocation component and ATP hydr...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2016.06.008

    authors: Josts I,Almeida Hernandez Y,Andreeva A,Tidow H

    更新日期:2016-07-21 00:00:00

  • Site-Specific Photo-Crosslinking Proteomics Reveal Regulation of IFITM3 Trafficking and Turnover by VCP/p97 ATPase.

    abstract::Interferon-induced transmembrane protein 3 (IFITM3) is a key interferon effector that broadly prevents infection by diverse viruses. However, the cellular factors that control IFITM3 homeostasis and antiviral activity have not been fully elucidated. Using site-specific photo-crosslinking and quantitative proteomic ana...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2020.03.004

    authors: Wu X,Spence JS,Das T,Yuan X,Chen C,Zhang Y,Li Y,Sun Y,Chandran K,Hang HC,Peng T

    更新日期:2020-05-21 00:00:00

  • Role of Thiol Reactivity for Targeting Mutant p53.

    abstract::Reactivation of mutant p53 has emerged as a promising approach for cancer therapy. Recent studies have identified several mutant p53-reactivating compounds that target thiol groups in mutant p53. Here we have investigated the relationship between thiol reactivity, p53 thermostabilization, mutant p53 refolding, mutant ...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2018.06.013

    authors: Zhang Q,Bergman J,Wiman KG,Bykov VJN

    更新日期:2018-10-18 00:00:00

  • Combined Proteomic and In Silico Target Identification Reveal a Role for 5-Lipoxygenase in Developmental Signaling Pathways.

    abstract::Identification and validation of the targets of bioactive small molecules identified in cell-based screening is challenging and often meets with failure, calling for the development of new methodology. We demonstrate that a combination of chemical proteomics with in silico target prediction employing the SPiDER method...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2018.05.016

    authors: Brand S,Roy S,Schröder P,Rathmer B,Roos J,Kapoor S,Patil S,Pommerenke C,Maier T,Janning P,Eberth S,Steinhilber D,Schade D,Schneider G,Kumar K,Ziegler S,Waldmann H

    更新日期:2018-09-20 00:00:00

  • Rox, a Rifamycin Resistance Enzyme with an Unprecedented Mechanism of Action.

    abstract::Rifamycin monooxygenases (Rox) are present in a variety of environmental bacteria and are associated with decomposition of the clinically utilized antibiotic rifampin. Here we report the structure and function of a drug-inducible rox gene from Streptomyces venezuelae, which encodes a class A flavoprotein monooxygenase...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2018.01.009

    authors: Koteva K,Cox G,Kelso JK,Surette MD,Zubyk HL,Ejim L,Stogios P,Savchenko A,Sørensen D,Wright GD

    更新日期:2018-04-19 00:00:00

  • Dawn of a New Era of Targeted Antioxidant Therapies.

    abstract::In this issue of Cell Chemical Biology, Shah et al. (2019) report an in vitro, high-throughput assay that predicts the ability of compounds to suppress peroxidation of phospholipids. This approach provides a way to design and optimize targeted antioxidants that suppress specific oxidative event in cells, potentially o...

    journal_title:Cell chemical biology

    pub_type: 评论,杂志文章

    doi:10.1016/j.chembiol.2019.11.003

    authors: Stockwell BR

    更新日期:2019-11-21 00:00:00

  • Ubiquinone Biosynthetic Complexes in Prokaryotes and Eukaryotes.

    abstract::Ubiquinone (UQ) is a conserved polyprenylated lipid essential to cellular respiration. Two papers, one in this issue of Cell Chemical Biology (Hajj Chehade et al., 2019) and another in Molecular Cell (Lohman et al., 2019), identify lipid-binding proteins that play crucial roles in chaperoning UQ-intermediates. ...

    journal_title:Cell chemical biology

    pub_type: 评论,杂志文章

    doi:10.1016/j.chembiol.2019.04.005

    authors: Tsui HS,Clarke CF

    更新日期:2019-04-18 00:00:00

  • Molecular Basis for Redox Activation of Epidermal Growth Factor Receptor Kinase.

    abstract::Epidermal growth factor receptor (EGFR) is a target of signal-derived H2O2, and oxidation of active-site cysteine 797 to sulfenic acid enhances kinase activity. Although a major class of covalent drugs targets C797, nothing is known about its catalytic importance or how S-sulfenylation leads to activation. Here, we re...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2016.05.017

    authors: Truong TH,Ung PM,Palde PB,Paulsen CE,Schlessinger A,Carroll KS

    更新日期:2016-07-21 00:00:00

  • Monstrous Mycobacterial Lipids.

    abstract::When it comes to lipid diversity, no bacterial genus approaches Mycobacterium. In this issue of Cell Chemical Biology, Burbaud et al. (2016) provide a multi-genic working model for the biosynthesis of trehalose polyphleate (TPP), one of the largest known lipids in mycobacteria. They demonstrate that this lipid is made...

    journal_title:Cell chemical biology

    pub_type: 评论,杂志文章

    doi:10.1016/j.chembiol.2016.02.004

    authors: Seeliger J,Moody DB

    更新日期:2016-02-18 00:00:00

  • Robust Prediction of Resistance to Trimethoprim in Staphylococcus aureus.

    abstract::The rise of antibiotic resistance threatens modern medicine; to combat it new diagnostic methods are required. Sequencing the whole genome of a pathogen offers the potential to accurately determine which antibiotics will be effective to treat a patient. A key limitation of this approach is that it cannot classify rare...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2017.12.009

    authors: Fowler PW,Cole K,Gordon NC,Kearns AM,Llewelyn MJ,Peto TEA,Crook DW,Walker AS

    更新日期:2018-03-15 00:00:00

  • Posttranslational Peptide-Modification Enzymes in Action: Key Roles for Leaders and Glutamate.

    abstract::In this issue of Cell Chemical Biology, Ortega et al. (2016) determine the structure of another lantibiotic dehydratase with a tRNA(Glu)-dependent mechanism of modification. Moreover, they identify a common recognition motif involved in leader peptide binding in a number of different peptide-modification enzymes. Thes...

    journal_title:Cell chemical biology

    pub_type: 评论,杂志文章

    doi:10.1016/j.chembiol.2016.03.001

    authors: Montalbán-López M,Kuipers OP

    更新日期:2016-03-17 00:00:00

  • Conformation Selective Antibody Enables Genome Profiling and Leads to Discovery of Parallel G-Quadruplex in Human Telomeres.

    abstract::G-quadruplexes are specialized secondary structures in nucleic acids that possess significant conformational polymorphisms. The precise G-quadruplex conformations in vivo and their relevance to biological functions remain controversial and unclear, especially for telomeric G-quadruplexes. Here, we report a novel singl...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2016.08.013

    authors: Liu HY,Zhao Q,Zhang TP,Wu Y,Xiong YX,Wang SK,Ge YL,He JH,Lv P,Ou TM,Tan JH,Li D,Gu LQ,Ren J,Zhao Y,Huang ZS

    更新日期:2016-10-20 00:00:00

  • Concise Chemoenzymatic Total Synthesis and Identification of Cellular Targets of Cepafungin I.

    abstract::The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to p...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2020.07.012

    authors: Amatuni A,Shuster A,Adibekian A,Renata H

    更新日期:2020-10-15 00:00:00

  • Small-Molecule Allosteric Triggers of Clostridium difficile Toxin B Auto-proteolysis as a Therapeutic Strategy.

    abstract::Clostridium difficile causes increasing numbers of life-threatening intestinal infections. Symptoms associated with C. difficile infection (CDI) are mediated by secreted protein toxins, whose virulence is modulated by intracellular auto-proteolysis following allosteric activation of their protease domains by inositol ...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2018.10.002

    authors: Ivarsson ME,Durantie E,Huberli C,Huwiler S,Hegde C,Friedman J,Altamura F,Lu J,Verdu EF,Bercik P,Logan SM,Chen W,Leroux JC,Castagner B

    更新日期:2019-01-17 00:00:00

  • GNF-2 Inhibits Dengue Virus by Targeting Abl Kinases and the Viral E Protein.

    abstract::Dengue virus infects more than 300 million people annually, yet there is no widely protective vaccine or drugs against the virus. Efforts to develop antivirals against classical targets such as the viral protease and polymerase have not yielded drugs that have advanced to the clinic. Here, we show that the allosteric ...

    journal_title:Cell chemical biology

    pub_type: 杂志文章

    doi:10.1016/j.chembiol.2016.03.010

    authors: Clark MJ,Miduturu C,Schmidt AG,Zhu X,Pitts JD,Wang J,Potisopon S,Zhang J,Wojciechowski A,Hann Chu JJ,Gray NS,Yang PL

    更新日期:2016-04-21 00:00:00