Last update 01 Nov 2024

Demethylmenaquinone methyltransferase

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with Demethylmenaquinone methyltransferase

GSK-1733953A

Target

Demethylmenaquinone methyltransferase

Mechanism

Demethylmenaquinone methyltransferase inhibitors

Active Org.-

Originator Org.

GSK Plc

Active Indication-

Inactive Indication

Tuberculosis

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Demethylmenaquinone methyltransferase

100 Translational Medicine associated with Demethylmenaquinone methyltransferase

0 Patents (Medical) associated with Demethylmenaquinone methyltransferase

Literatures (Medical) associated with Demethylmenaquinone methyltransferase

01 Feb 2020·Nature ChemistryQ1 · CHEMISTRY

Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms

Q1 · CHEMISTRY

Article

Author: Rohde, Manfred ; Hacker, Stephan M ; Chaves-Moreno, Diego ; Ugur, Ilke ; Wuest, William M ; Fetzer, Christian ; Rox, Katharina ; Jennings, Megan C ; Antes, Iris ; Lehmann, Johannes ; Pieper, Dietmar H ; Korotkov, Vadim S ; Medina, Eva ; Mandl, Franziska A M ; Sieber, Stephan A ; Kunold, Elena ; Hackl, Mathias W ; Macsics, Robert ; Le, Philipp ; Kuster, Bernhard ; Reinecke, Maria

New drugs are desperately needed to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report screening commercial kinase inhibitors for antibacterial activity and found the anticancer drug sorafenib as major hit that effectively kills MRSA strains. Varying the key structural features led to the identification of a potent analogue, PK150, that showed antibacterial activity against several pathogenic strains at submicromolar concentrations. Furthermore, this antibiotic eliminated challenging persisters as well as established biofilms. PK150 holds promising therapeutic potential as it did not induce in vitro resistance, and shows oral bioavailability and in vivo efficacy. Analysis of the mode of action using chemical proteomics revealed several targets, which included interference with menaquinone biosynthesis by inhibiting demethylmenaquinone methyltransferase and the stimulation of protein secretion by altering the activity of signal peptidase IB. Reduced endogenous menaquinone levels along with enhanced levels of extracellular proteins of PK150-treated bacteria support this target hypothesis. The associated antibiotic effects, especially the lack of resistance development, probably stem from the compound's polypharmacology.

RSC AdvancesQ3 · CHEMISTRY

Thompson loop: opportunities for antitubercular drug design by targeting the weak spot in demethylmenaquinone methyltransferase protein

Q3 · CHEMISTRY

ArticleOA

Author: Adewumi, Adeniyi T. ; Soremekun, Opeyemi S. ; Soliman, Mahmoud E. S. ; Ajadi, Mary B.

Graphical superimposed snapshots of the Thompson novel loop (yellow) ofmenGprotein: apo (A) and bound (B) systems. The loop switches between open and closed conformations; critical for therapeutic activity.

PeerJQ3 · BIOLOGY

Analysis of the infant gut microbiome reveals metabolic functional roles associated with healthy infants and infants with atopic dermatitis using metaproteomics

Q3 · BIOLOGY

ArticleOA

Author: Kingkaw, Amornthep ; Suratannon, Narissara ; Wongoutong, Chantha ; Nakphaichit, Massalin ; Nitisinprasert, Sunee ; Vongsangnak, Wanwipa ; Chatchatee, Pantipa ; Krobthong, Sucheewin ; Charoenlappanit, Sawanya ; Roytrakul, Sittiruk

The infant gut microbiome consists of a complex and diverse microbial community. Comprehensive taxonomic and metabolic functional knowledge about microbial communities supports medical and biological applications, such as fecal diagnostics. Among the omics approaches available for the investigation of microbial communities, metaproteomics-based analysis is a very powerful approach; under this method, the activity of microbial communities is explored by investigating protein expression within a sample. Through use of metaproteomics, this study aimed to investigate the microbial community composition of the infant gut to identify different key proteins playing metabolic functional roles in the microbiome of healthy infants and infants with atopic dermatitis in a Thai population-based birth cohort. Here, 18 fecal samples were analyzed by liquid chromatography-tandem mass spectrometry to conduct taxonomic, functional, and pathway-based protein annotation. Accordingly, 49,973 annotated proteins out of 68,232 total proteins were investigated in gut microbiome samples and compared between the healthy and atopic dermatitis groups. Through differentially expressed proteins (DEPs) analysis, 130 significant DEPs were identified between the healthy and atopic dermatitis groups. Among these DEPs, eight significant proteins were uniquely expressed in the atopic dermatitis group. For instance, triosephosphate isomerase (TPI) inBifidobacteriaceaein the genusAlloscardoviaand demethylmenaquinone methyltransferase (DMM) inBacteroideswere shown to potentially play metabolic functional roles related to disease. PPI network analysis revealed seven reporter proteins showing metabolic alterations between the healthy and disease groups associated with the biosynthesis of ubiquinone and other quinones as well as the energy supply. This study serves as a scaffold for microbial community-wide metabolic functional studies of the infant gut microbiome in relation to allergic disease.

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Demethylmenaquinone methyltransferase

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