keyword
MENU ▼
Read by QxMD icon Read
search

thioesterase

keyword
https://www.readbyqxmd.com/read/29155429/monobactam-formation-in-sulfazecin-by-a-nonribosomal-peptide-synthetase-thioesterase
#1
Ryan A Oliver, Rongfeng Li, Craig A Townsend
The N-sulfonated monocyclic β-lactam ring characteristic of the monobactams confers resistance to zinc metallo-β-lactamases and affords the most effective class to combat carbapenem-resistant enterobacteria (CRE). Here we report unprecedented nonribosomal peptide synthetase activities, wherein an assembled tripeptide is N-sulfonated in trans before direct synthesis of the β-lactam ring in a noncanonical, cysteine-containing thioesterase domain. This means of azetidinone synthesis is distinct from the three others known in nature...
November 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29023093/a-fluorescent-probe-with-improved-water-solubility-permits-the-analysis-of-protein-s-depalmitoylation-activity-in-live-cells
#2
Tian Qiu, Rahul S Kathayat, Yang Cao, Michael William Beck, Bryan C Dickinson
S-palmitoylation is an abundant lipid post-translational modification (PTM) that is dynamically installed on and removed from target proteins to regulate their activity and cellular localization. A dearth of tools to study the activities and regulation of protein S-depalmitoylases - thioesterase "erasers" of protein cysteine S-palmitoylation - has contributed to an incomplete understanding of the role of dynamic S-palmitoylation in regulating proteome lipidation. Recently, we developed "depalmitoylation probes" (DPPs), small molecule probes that become fluorescent upon S-depalmitoylase enzymatic activity...
October 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28991437/structural-insight-into-acyl-acp-thioesterase-toward-substrate-specificity-design
#3
Yanbin Feng, Yayue Wang, Jiao Liu, Yinghui Liu, Xupeng Cao, Song Xue
Acyl-ACP thioesterase (TE) catalyzes the hydrolysis of thioester bonds during type II fatty acid synthesis and directly determines fatty acid chain length. Most TEs are responsible for recognition of 16:0 and 18:1 substrates, while specific TEs interrupt acyl-ACP elongation at C8-C14. However, the acyl selection mechanism of TE has not been thoroughly elucidated to date. In this study, the crystal structure of the C12-specific thioesterase FatB from Umbellularia californica, which consists of two independent hotdog domains, was determined...
November 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28976546/effect-of-nadph-availability-on-free-fatty-acid-production-in-escherichia-coli
#4
Wei Li, Hui Wu, Mai Li, Ka-Yiu San
Microbial conversion of renewable carbon sources to free fatty acids has attracted significant attention in recent years. Accumulation of free fatty acids in Escherichia coli by overexpression of an acyl-ACP thioesterase which can break the fatty acid elongation has been well established. Various efforts have been made to increase fatty acid production in E. coli by enhancing the enzymes involved in the fatty acid synthesis cycle or host strain manipulations. The current study focused on the effect of NADPH availability on free fatty acids (FFAs) productivity...
October 4, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28972175/structural-insights-into-gdp-mediated-regulation-of-a-bacterial-acyl-coa-thioesterase
#5
Yogesh B Khandokar, Parul Srivastava, Nathan Cowieson, Subir Sarker, David Aragao, Shubagata Das, Kate M Smith, Shane R Raidal, Jade K Forwood
Thioesterases catalyze the cleavage of thioester bonds within many activated fatty acids and acyl-CoA substrates. They are expressed ubiquitously in both prokaryotes and eukaryotes and are subdivided into 25 thioesterase families according to their catalytic active site, protein oligomerization, and substrate specificity. While many of these enzyme families are well characterized in terms of function and substrate specificity, regulation across most thioesterase families is poorly understood. Here, we characterized a TE6 thioesterase from the bacterium Neisseria meningitidis...
October 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28955734/chronic-high-fat-feeding-impairs-adaptive-induction-of-mitochondrial-fatty-acid-combustion-associated-proteins-in-brown-adipose-tissue-of-mice
#6
Takayuki Ohtomo, Kanako Ino, Ryota Miyashita, Maya Chigira, Masahiko Nakamura, Koji Someya, Niro Inaba, Mariko Fujita, Mitsuhiro Takagi, Junji Yamada
Since brown adipose tissue (BAT) is involved in thermogenesis using fatty acids as a fuel, BAT activation is a potential strategy for treating obesity and diabetes. However, whether BAT fatty acid combusting capacity is preserved in these conditions has remained unclear. We therefore evaluated expression levels of fatty acid oxidation-associated enzymes and uncoupling protein 1 (Ucp1) in BAT by western blot using a diet-induced obesity C57BL/6J mouse model. In C57BL/6J mice fed a high-fat diet (HFD) over 2-4 weeks, carnitine palmitoyltransferase 2 (Cpt2), acyl-CoA thioesterase (Acot) 2, Acot11 and Ucp1 levels were significantly increased compared with baseline and control low-fat diet (LFD)-fed mice...
July 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28943460/engineering-a-bacterial-platform-for-total-biosynthesis-of-caffeic-acid-derived-phenethyl-esters-and-amides
#7
Jian Wang, Monika Mahajani, Sheneika L Jackson, Yaping Yang, Mengyin Chen, Eric M Ferreira, Yuheng Lin, Yajun Yan
Caffeic acid has been widely recognized as a versatile pharmacophore for synthesis of new chemical entities, among which caffeic acid derived phenethyl esters and amides are the most extensively-investigated bioactive compounds with potential therapeutical applications. However, the natural biosynthetic routes for caffeic acid derived phenethyl esters or amides remain enigmatic, limiting their bio-based production. Herein, product-directed design of biosynthetic schemes allowed the development of thermodynamically favorable pathways for these compounds via acyltransferase (ATF) mediated trans-esterification...
September 21, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28928723/analysis-of-the-sequences-structures-and-functions-of-product-releasing-enzyme-domains-in-fungal-polyketide-synthases
#8
Lu Liu, Zheng Zhang, Chang-Lun Shao, Chang-Yun Wang
Product-releasing enzyme (PRE) domains in fungal non-reducing polyketide synthases (NR-PKSs) play a crucial role in catalysis and editing during polyketide biosynthesis, especially accelerating final biosynthetic reactions accompanied with product offloading. However, up to date, the systematic knowledge about PRE domains is deficient. In the present study, the relationships between sequences, structures, and functions of PRE domains were analyzed with 574 NR-PKSs of eight groups (I-VIII). It was found that the PRE domains in NR-PKSs could be mainly classified into three types, thioesterase (TE), reductase (R), and metallo-β-lactamase-type TE (MβL-TE)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28927126/overexpression-and-proliferation-dependence-of-acyl-coa-thioesterase-11-and-13-in-lung-adenocarcinoma
#9
Jen-Yu Hung, Shyh-Ren Chiang, Kuan-Ting Liu, Ming-Ju Tsai, Ming-Shyan Huang, Jiunn-Min Shieh, Meng-Chi Yen, Ya-Ling Hsu
The metabolites of fatty acyl-Coenzyme A (CoA) and metabolic enzymes contribute to lipid biosynthesis, signal transduction, and gene transcription. Previous studies have indicated that elevated concentrations of specific free fatty acids in the plasma and overexpression of specific fatty acyl-CoA metabolic enzymes are observed in patients with lung adenocarcinoma. However, there are >30 enzymes in this metabolic network and have been fully investigated. In the present study, the expression levels of enzymes in the acyl-CoA synthetase (ACS) and acyl-CoA thioesterase (ACOT) families were analyzed from six microarray expression datasets that were collected from Gene Expression Omnibus...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28899863/a-unified-approach-to-targeting-the-lysosome-s-degradative-and-growth-signaling-roles
#10
Vito W Rebecca, Michael C Nicastri, Noel McLaughlin, Colin Fennelly, Quentin McAfee, Amruta Ronghe, Michel Nofal, Chun-Yan Lim, Eric Witze, Cynthia I Chude, Gao Zhang, Gretchen M Alicea, Shengfu Piao, Sengottuvelan Murugan, Rani Ojha, Samuel M Levi, Zhi Wei, Julie S Barber-Rotenberg, Maureen E Murphy, Gordon B Mills, Yiling Lu, Joshua Rabinowitz, Ronen Marmorstein, Qin Liu, Shujing Liu, Xiaowei Xu, Meenhard Herlyn, Roberto Zoncu, Donita C Brady, David W Speicher, Jeffrey D Winkler, Ravi K Amaravadi
Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e., autophagy and macropinocytosis) while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQ) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy...
November 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28884166/crystal-structure-of-thioesterase-sgce10-supporting-common-polyene-intermediates-in-9-and-10-membered-enediyne-core-biosynthesis
#11
Thibault Annaval, Jeffrey D Rudolf, Chin-Yuan Chang, Jeremy R Lohman, Youngchang Kim, Lance Bigelow, Robert Jedrzejczak, Gyorgy Babnigg, Andrzej Joachimiak, George N Phillips, Ben Shen
Enediynes are potent natural product anticancer antibiotics, and are classified as 9- or 10-membered according to the size of their enediyne core carbon skeleton. Both 9- and 10-membered enediyne cores are biosynthesized by the enediyne polyketide synthase (PKSE), thioesterase (TE), and PKSE-associated enzymes. Although the divergence between 9- and 10-membered enediyne core biosynthesis remains unclear, it has been observed that nascent polyketide intermediates, tethered to the acyl carrier protein (ACP) domain of PKSE, could be released by TE in the absence of the PKSE-associated enzymes...
August 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28878621/the-networks-of-genes-encoding-palmitoylated-proteins-in-axonal-and-synaptic-compartments-are-affected-in-ppt1-overexpressing-neuronal-like-cells
#12
Francesco Pezzini, Marzia Bianchi, Salvatore Benfatto, Francesca Griggio, Stefano Doccini, Rosalba Carrozzo, Arvydas Dapkunas, Massimo Delledonne, Filippo M Santorelli, Maciej M Lalowski, Alessandro Simonati
CLN1 disease (OMIM #256730) is an early childhood ceroid-lipofuscinosis associated with mutated CLN1, whose product Palmitoyl-Protein Thioesterase 1 (PPT1) is a lysosomal enzyme involved in the removal of palmitate residues from S-acylated proteins. In neurons, PPT1 expression is also linked to synaptic compartments. The aim of this study was to unravel molecular signatures connected to CLN1. We utilized SH-SY5Y neuroblastoma cells overexpressing wild type CLN1 (SH-p.wtCLN1) and five selected CLN1 patients' mutations...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28846367/structure-and-functional-analysis-of-clbq-an-unusual-intermediate-releasing-thioesterase-from-the-colibactin-biosynthetic-pathway
#13
Naga Sandhya Guntaka, Alan R Healy, Jason M Crawford, Seth B Herzon, Steven D Bruner
Colibactin is a genotoxic hybrid nonribosomal peptide/polyketide secondary metabolite produced by various pathogenic and probiotic bacteria residing in the human gut. The presence of colibactin metabolites has been correlated to colorectal cancer formation in several studies. The specific function of many gene products in the colibactin gene cluster can be predicted. However, the role of ClbQ, a type II editing thioesterase, has not been established. The importance of ClbQ has been demonstrated by genetic deletions that abolish colibactin cytotoxic activity, and recent studies suggest an atypical role in releasing pathway intermediates from the assembly line...
September 8, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28836772/identification-of-a-thioesterase-bottleneck-in-the-pikromycin-pathway-through-full-module-processing-of-unnatural-pentaketides
#14
Douglas A Hansen, Aaron A Koch, David H Sherman
Polyketide biosynthetic pathways have been engineered to generate natural product analogs for over two decades. However, manipulation of modular type I polyketide synthases (PKSs) to make unnatural metabolites commonly results in attenuated yields or entirely inactive pathways, and the mechanistic basis for compromised production is rarely elucidated since rate-limiting or inactive domain(s) remain unidentified. Accordingly, we synthesized and assayed a series of modified pikromycin (Pik) pentaketides that mimic early pathway engineering to probe the substrate tolerance of the PikAIII-TE module in vitro...
September 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28836768/a-single-active-site-mutation-in-the-pikromycin-thioesterase-generates-a-more-effective-macrocyclization-catalyst
#15
Aaron A Koch, Douglas A Hansen, Vikram V Shende, Lawrence R Furan, K N Houk, Gonzalo Jiménez-Osés, David H Sherman
Macrolactonization of natural product analogs presents a significant challenge to both biosynthetic assembly and synthetic chemistry. In the preceding paper , we identified a thioesterase (TE) domain catalytic bottleneck processing unnatural substrates in the pikromycin (Pik) system, preventing the formation of epimerized macrolactones. Here, we perform molecular dynamics simulations showing the epimerized hexaketide was accommodated within the Pik TE active site; however, intrinsic conformational preferences of the substrate resulted in predominately unproductive conformations, in agreement with the observed hydrolysis...
September 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28826475/identification-and-dynamics-of-the-human-zdhhc16-zdhhc6-palmitoylation-cascade
#16
Laurence Abrami, Tiziano Dallavilla, Patrick A Sandoz, Mustafa Demir, Béatrice Kunz, Georgios Savoglidis, Vassily Hatzimanikatis, F Gisou van der Goot
S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC palmitoyltransferase family is still limited. Here we show that human ZDHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, ZDHHC16, revealing the first palmitoylation cascade. The combination of site specific mutagenesis of the three ZDHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the eight differentially palmitoylated ZDHHC6 species...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28814974/time-resolved-transcriptome-analysis-and-lipid-pathway-reconstruction-of-the-oleaginous-green-microalga-monoraphidium-neglectum-reveal-a-model-for-triacylglycerol-and-lipid-hyperaccumulation
#17
Daniel Jaeger, Anika Winkler, Jan H Mussgnug, Jörn Kalinowski, Alexander Goesmann, Olaf Kruse
BACKGROUND: Oleaginous microalgae are promising production hosts for the sustainable generation of lipid-based bioproducts and as bioenergy carriers such as biodiesel. Transcriptomics of the lipid accumulation phase, triggered efficiently by nitrogen starvation, is a valuable approach for the identification of gene targets for metabolic engineering. RESULTS: An explorative analysis of the detailed transcriptional response to different stages of nitrogen availability was performed in the oleaginous green alga Monoraphidium neglectum...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28792770/proteomic-analysis-of-brain-and-cerebrospinal-fluid-from-the-three-major-forms-of-neuronal-ceroid-lipofuscinosis-reveals-potential-biomarkers
#18
David E Sleat, Abla Tannous, Istvan Sohar, Jennifer A Wiseman, Haiyan Zheng, Meiqian Qian, Caifeng Zhao, Winnie Xin, Rosemary Barone, Katherine B Sims, Dirk F Moore, Peter Lobel
Clinical trials have been conducted for the neuronal ceroid lipofuscinoses (NCLs), a group of neurodegenerative lysosomal diseases that primarily affect children. Whereas clinical rating systems will evaluate long-term efficacy, biomarkers to measure short-term response to treatment would be extremely valuable. To identify candidate biomarkers, we analyzed autopsy brain and matching CSF samples from controls and three genetically distinct NCLs due to deficiencies in palmitoyl protein thioesterase 1 (CLN1 disease), tripeptidyl peptidase 1 (CLN2 disease), and CLN3 protein (CLN3 disease)...
August 28, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28769963/tissue-specific-floral-transcriptome-analysis-of-the-sexually-deceptive-orchid-chiloglottis-trapeziformis-provides-insights-into-the-biosynthesis-and-regulation-of-its-unique-uv-b-dependent-floral-volatile-chiloglottone-1
#19
Darren C J Wong, Ranamalie Amarasinghe, Claudia Rodriguez-Delgado, Rodney Eyles, Eran Pichersky, Rod Peakall
The Australian sexually deceptive orchid, Chiloglottis trapeziformis, employs a unique UV-B-dependent floral volatile, chiloglottone 1, for specific male wasp pollinator attraction. Chiloglottone 1 and related variants (2,5-dialkylcyclohexane-1,3-diones), represent a unique class of specialized metabolites presumed to be the product of cyclization between two fatty acid (FA) precursors. However, the genes involved in the biosynthesis of precursors, intermediates, and transcriptional regulation remains to be discovered...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28741300/catalytic-mechanism-of-the-hotdog-fold-thioesterase-pa1618-revealed-by-x-ray-structure-determination-of-a-substrate-bound-oxygen-ester-analogue-complex
#20
John A Latham, Tianyang Ji, Kaila Matthews, Patrick S Mariano, Karen N Allen, Debra Dunaway-Mariano
Thioesterase activity accounts for the majority of the activities in the hotdog-fold superfamily. The structures and mechanisms of catalysis for many hotdog enzymes have been elucidated by X-ray crystallography and kinetics to probe the specific substrate usage and cellular functions. However, structures of hotdog thioesterases in complexes with substrate analogues reported to date utilize ligands that either represent truncations of the substrate or include additional atoms to prevent hydrolysis. Here we present the synthesis of an isosteric and isoelectronic substrate analogue-benzoyl-OdCoA-and the X-ray crystal structure of a complex of the analogue with Pseudomonas aeruginosa hotdog thioesterase PA1618 (at 1...
October 5, 2017: Chembiochem: a European Journal of Chemical Biology
keyword
keyword
51857
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"