Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan

Biochemistry
W H WardI W Taylor

Abstract

Triclosan is used widely as an antibacterial agent in dermatological products, mouthwashes, and toothpastes. Recent studies imply that antibacterial activity results from binding to enoyl (acyl carrier protein) reductase (EACPR, EC 1.3.1.9). We first recognized the ability of triclosan to inhibit EACPR from Escherichia coli in a high throughput screen where the enzyme and test compound were preincubated with NAD(+), which is a product of the reaction. The concentration of triclosan required for 50% inhibition approximates to 50% of the enzyme concentration, indicating that the free compound is depleted by binding to EACPR. With no preincubation or added NAD(+), the degree of inhibition by 150 nM triclosan increases gradually over several minutes. The onset of inhibition is more rapid when NAD(+) is added. Gel filtration and mass spectrometry show that inhibition by triclosan is reversible. Steady-state assays were designed to avoid depletion of free inhibitor and changes in the degree of inhibition. The results suggest that triclosan binds to E-NAD(+) complex, with a dissociation constant around 20-40 pM. Triclosan follows competitive kinetics with respect to NADH, giving an inhibition constant of 38 pM at zero NADH and saturat...Continue Reading

References

Jun 14, 1996·Biochemical Pharmacology·W H WardM A Eakin
Nov 7, 1998·The Journal of Biological Chemistry·R J HeathC O Rock
Apr 10, 1999·The Journal of Biological Chemistry·R J HeathC O Rock
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4

❮ Previous
Next ❯

Citations

Mar 5, 2003·Journal of Molecular Biology·Tomi T AirenneJ Kalervo Hiltunen
Oct 10, 2001·Progress in Lipid Research·R J HeathC O Rock
Aug 25, 2010·Quarterly Reviews of Biophysics·Timm MaierNenad Ban
Jan 16, 2008·Accounts of Chemical Research·Hao Lu, Peter J Tonge
May 19, 2011·The Journal of Antibiotics·Mark S Butler, Matthew A Cooper
Mar 14, 2009·The Journal of Antimicrobial Chemotherapy·Chang Ji ZhengWon-Gon Kim
Sep 8, 2009·The Journal of Antimicrobial Chemotherapy·Kathleen EnglandRichard A Slayden
Mar 12, 2011·The Journal of Antimicrobial Chemotherapy·Nina LiuPeter J Tonge
Aug 23, 2002·Protein Science : a Publication of the Protein Society·Christopher A BottomsJohn J Tanner
Oct 18, 2002·Antimicrobial Agents and Chemotherapy·Frank FanDavid J Payne
Apr 15, 2003·Clinical Microbiology Reviews·Peter Gilbert, Andrew J McBain
Dec 12, 2001·Biochemical and Biophysical Research Communications·M KapoorN Surolia
Oct 13, 2015·International Journal of Molecular Sciences·Camilo Henrique da Silva LimaMagaly Girão Albuquerque
Nov 11, 2014·Journal of Enzyme Inhibition and Medicinal Chemistry·Ondrej HolasMartin Dolezal
Dec 20, 2008·Protein Expression and Purification·Lisa WenAshish K Pathak
Oct 25, 2008·Current Opinion in Structural Biology·Marc LeibundgutNenad Ban
Sep 26, 2007·Bioorganic & Medicinal Chemistry·Tomohiro OzawaKeiko Yamada
Aug 29, 2007·Bioorganic & Medicinal Chemistry·Xin HePaul R Ortiz de Montellano
Jun 30, 2007·Bioorganic & Medicinal Chemistry Letters·Hideo KitagawaMaiko Iida
Feb 13, 2007·Bioorganic & Medicinal Chemistry·Yves L Janin
Nov 11, 2006·Bioorganic & Medicinal Chemistry·Hideo KitagawaKunio Atsumi
Mar 5, 2016·Journal of the American Chemical Society·Lorillee TallorinMichael D Burkart
Sep 13, 2012·Protein Science : a Publication of the Protein Society·Steffen Lindert, J Andrew McCammon
Dec 14, 2011·Basic & Clinical Pharmacology & Toxicology·Perinkulam Ravi DeepaSubramanian Krishnakumar
Dec 3, 2002·Biochemical and Biophysical Research Communications·Il-Han LeeJeong K Lee
Sep 24, 2004·Journal of Molecular Biology·Lakshmi Swarnamukhi PiduguKaza Suguna
Sep 15, 2015·Journal of Ethnopharmacology·Jian-Hui LiuQi Tan
Mar 5, 2013·Bioorganic & Medicinal Chemistry Letters·Gang ChengRima McLeod

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.