Read by QxMD icon Read


Elisa Bellomo, Asma Abro, Christer Hogstrand, Wolfgang Maret, Carmen Domene
Whilst the majority of phosphatases are metalloenzymes, the prevailing model for the reactions catalyzed by protein tyrosine phosphatases does not involve any metal ion. Yet, both metal cations and oxoanions affect their enzymatic activity. Mg2+ and Zn2+ activate and inhibit, respectively, protein tyrosine phosphatase 1B (PTP1B). Molecular dynamics simulations, metadynamics and quantum chemical calculations in combination with experimental investigations demonstrate that Mg2+ and Zn2+ compete for the same binding site in the active site only in the closed conformation of the enzyme in its phosphorylated state...
March 7, 2018: Journal of the American Chemical Society
Tsuyoshi Tanimoto
 Aldose reductase (AR) is involved in the pathogenesis of complications in diabetes. In this study, the enzymatic properties of AR isolated from various sources and a recombinant human AR (rh-AR) were analyzed in detail. The sensitivity of different forms of AR to several AR inhibitors (ARIs) was compared. Our findings enabled us to propose that human AR should be used as the target enzyme in the development of ARIs. An enzyme-linked immunosorbent assay (ELISA) for human AR which employed monoclonal antibodies against rh-AR was created, and this method was used to demonstrate the distribution of AR in human tissues...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Md Saiful Islam, Thomas M Leissing, Rasheduzzaman Chowdhury, Richard J Hopkinson, Christopher J Schofield
2-Oxoglutarate (2OG)-dependent oxygenases (2OGXs) catalyze a remarkably diverse range of oxidative reactions. In animals, these comprise hydroxylations and N-demethylations proceeding via hydroxylation; in plants and microbes, they catalyze a wider range including ring formations, rearrangements, desaturations, and halogenations. The catalytic flexibility of 2OGXs is reflected in their biological functions. After pioneering work identified the roles of 2OGXs in collagen biosynthesis, research indicated they also function in plant and animal development, transcriptional regulation, nucleic acid modification/repair, fatty acid metabolism, and secondary metabolite biosynthesis, including of medicinally important antibiotics...
March 1, 2018: Annual Review of Biochemistry
A E Naas, L M Solden, A D Norbeck, H Brewer, L H Hagen, I M Heggenes, A C McHardy, R I Mackie, L Paša-Tolić, M Ø Arntzen, V G H Eijsink, N M Koropatkin, M Hess, K C Wrighton, P B Pope
BACKGROUND: In nature, obligate herbivorous ruminants have a close symbiotic relationship with their gastrointestinal microbiome, which proficiently deconstructs plant biomass. Despite decades of research, lignocellulose degradation in the rumen has thus far been attributed to a limited number of culturable microorganisms. Here, we combine meta-omics and enzymology to identify and describe a novel Bacteroidetes family ("Candidatus MH11") composed entirely of uncultivated strains that are predominant in ruminants and only distantly related to previously characterized taxa...
March 1, 2018: Microbiome
Marta A Garbacz, Scott A Lujan, Adam B Burkholder, Phillip B Cox, Qiuqin Wu, Zhi-Xiong Zhou, James E Haber, Thomas A Kunkel
To investigate nuclear DNA replication enzymology in vivo, we have studied Saccharomyces cerevisiae strains containing a pol2-16 mutation that inactivates the catalytic activities of DNA polymerase ε (Pol ε). Although pol2-16 mutants survive, they present very tiny spore colonies, increased doubling time, larger than normal cells, aberrant nuclei, and rapid acquisition of suppressor mutations. These phenotypes reveal a severe growth defect that is distinct from that of strains that lack only Pol ε proofreading (pol2-4), consistent with the idea that Pol ε is the major leading-strand polymerase used for unstressed DNA replication...
February 27, 2018: Nature Communications
Karin Julius, Samy R Al-Ayoubi, Michael Paulus, Metin Tolan, Roland Winter
Investigating the correlation between structure and activity of oligomeric enzymes at high pressure is essential for understanding intermolecular interactions and reactivity of proteins in cellulo of organisms thriving at extreme environmental conditions as well as for biotechnological applications, such as high-pressure enzymology. In a combined experimental effort employing small-angle X-ray scattering, FT-IR and fluorescence spectroscopy as well as stopped-flow enzyme kinetics in concert with high-pressure techniques, we reveal the pressure-induced conformational changes of the dimeric enzyme horse liver alcohol dehydrogenase (LADH) on the quaternary, secondary and tertiary structural level...
February 26, 2018: Physical Chemistry Chemical Physics: PCCP
Coral Y Zhou, Stephanie L Johnson, Laura J Lee, Adam D Longhurst, Sean L Beckwith, Matthew J Johnson, Ashby J Morrison, Geeta J Narlikar
The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60 bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20 bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation...
February 15, 2018: Molecular Cell
Jonathan S Gootenberg, Omar O Abudayyeh, Max J Kellner, Julia Joung, James J Collins, Feng Zhang
Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (<u>S</u>pecific<u>H</u>igh Sensitivity<u>E</u>nzymatic<u>R</u>eporter Un<u>LOCK</u>ing) that combines isothermal pre-amplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCKv2: 1) 4-channel single reaction multiplexing using orthogonal CRISPR enzymes; 2) quantitative measurement of input down to 2 aM; 3) 3...
February 15, 2018: Science
Shengchao Li, Weiping Zheng
Sirtuins are a family of intracellular enzymes whose enzymatic activities include catalyzing the β-nicotinamide adenine dinucleotide (β-NAD+)-dependent Nɛ-acyl-lysine deacylation and the β-NAD+-dependent mono-ADP-ribosylation. Among the seven sirtuin family members (i.e., SIRT1-7) thus far identified in mammals including humans, we know SIRT1/2/3/5/6 better than SIRT4/7 as for their enzymatic activities and the cellular roles of the reactions they catalyze. This chapter will provide an updated account on the enzymology and biology of SIRT4 and SIRT7, the two less well-understood mammalian sirtuins...
2018: Progress in Molecular Biology and Translational Science
Sascha Hein, Jonas von Irmer, Markus Gallei, Reinhard Meusinger, Jörg Simon
Dimethylmenaquinone (DMMK), a prevalent menaquinone (MK) derivative of uncertain function, is characteristic for members of the class Coriobacteriia. Such bacteria are frequently present in intestinal microbiomes and comprise several pathogenic species. The coriobacterial model organism Adlercreutzia equolifaciens was used to investigate the enzymology of DMMK biosynthesis. A HemN-like class C radical S-adenosylmethionine methyltransferase (MenK2) from A. equolifaciens was produced in Wolinella succinogenes or Escherichia coli cells and found to methylate MK specifically at position C-7...
February 3, 2018: Biochimica et Biophysica Acta
Pavel Kudrin, Ievgen Dzhygyr, Kensuke Ishiguro, Jelena Beljantseva, Elena Maksimova, Sofia Raquel Alves Oliveira, Vallo Varik, Roshani Payoe, Andrey L Konevega, Tanel Tenson, Tsutomu Suzuki, Vasili Hauryliuk
During amino acid starvation the Escherichia coli stringent response factor RelA recognizes deacylated tRNA in the ribosomal A-site. This interaction activates RelA-mediated synthesis of alarmone nucleotides pppGpp and ppGpp, collectively referred to as (p)ppGpp. These two alarmones are synthesized by addition of a pyrophosphate moiety to the 3' position of the abundant cellular nucleotide GTP and less abundant nucleotide GDP, respectively. Using untagged native RelA we show that allosteric activation of RelA by pppGpp increases the efficiency of GDP conversion to achieve the maximum rate of (p)ppGpp production...
January 30, 2018: Nucleic Acids Research
Jillian E Smith-Carpenter, Benjamin J Alper
Here we report the enzymologic characterization of recombinant human pitrilysin metallopeptidase 1 (Pitrm1) and derivative mutants including the arginine-to-glutamine substitution mutant Pitrm1 R183Q, which has been implicated in inherited amyloidogenic neuropathy. Recombinant Pitrm1 R183Q was readily expressed in and purified from E. coli, but was less active than the recombinant wild-type enzyme against recombinant amyloid beta peptide (Aβ 1-40). A novel fluorogenic substrate derived from the reported Aβ 1-40 core peptide cleavage sequence, Mca-KLVFFAEDK-(Dnp)-OH, was synthesized and applied to real-time kinetic study of Pitrm1 and derivative mutants including Pitrm1 R183Q...
January 31, 2018: Protein Science: a Publication of the Protein Society
Sara Calhoun, Magdalena Korczynska, Daniel J Wichelecki, Brian San Francisco, Suwen Zhao, Dmitry A Rodionov, Matthew W Vetting, Nawar F Al-Obaidi, Henry Lin, Matthew J O'Meara, David A Scott, John H Morris, Daniel Russel, Steven C Almo, Andrei L Osterman, John A Gerlt, Matthew P Jacobson, Brian K Shoichet, Andrej Sali
The functions of most proteins are yet to be determined. The function of an enzyme is often defined by its interacting partners, including its substrate and product, and its role in larger metabolic networks. Here, we describe a computational method that predicts the functions of orphan enzymes by organizing them into a linear metabolic pathway. Given candidate enzyme and metabolite pathway members, this aim is achieved by finding those pathways that satisfy structural and network restraints implied by varied input information, including that from virtual screening, chemoinformatics, genomic context analysis, and ligand -binding experiments...
January 29, 2018: ELife
Chunyi Tong, Chuan Zhao, Bin Liu, Bin Li, Zhaoyang Ai, Jialong Fan, Wei Wang
Except as an important object in theoretical and experimental studies in enzymology, RNase A also plays an important role in the development of many kinds of diseases by regulating various physiological or pathological processes including cell growth, proliferation, differentiation, and invasion et al. Thus, it can be used as a useful biomarker for the disease theranostics. Here, a simple, sensitive and low-cost assay for RNase A was constructed by combining a fluorogenic substrate with reduced graphene oxide (rGO)...
January 25, 2018: Analytical Chemistry
Huaixiu Wen, Bowen Tang, Alan J Stewart, Yanduo Tao, Yun Shao, Yulei Cui, Huilan Yue, Jinjin Pei, Zenggen Liu, Lijuan Mei, Ruitao Yu, Lei Jiang
Diabetes mellitus (DM) is a serious metabolic disorder, where impaired postprandial blood glucose regulation often leads to severe health complications. The natural chemical erythritol is a C4 polyol approved by the U.S. Food and Drug Administration for use as a sweetener. Here, we examined a potential role for erythritol in the control of postprandial blood glucose levels in DM. An anti-postprandial hyperglycemia effect upon erythritol administration (500 mg kg-1) was demonstrated in alloxan-induced DM model mice by monitoring changes in blood glucose after intragastric administration of drugs and starch...
February 5, 2018: Journal of Agricultural and Food Chemistry
Dhanaraju Mandalapu, Xinjian Ji, Jinfeng Chen, Chuchu Guo, Wan-Qiu Liu, Wei Ding, Jiahai Zhou, Qi Zhang
A chemoenzymatic approach for the synthesis of teixobactin analogues has been established by using the tandem thioesterase (TE) of the non-ribosomal peptide synthase (NRPS) Txo2. We show that, unlike the closely-related counterparts involved in lysobactin biosynthesis (in which the N-terminal TE is solely responsible for the lactonization reaction), the two teixobactin TE domains are functionally exchangeable and likely act synergistically, representing an unprecedented off-loading mechanism in NRPS enzymology...
January 23, 2018: Journal of Organic Chemistry
Elvira Romero, J Rubén Gómez Castellanos, Giovanni Gadda, Marco W Fraaije, Andrea Mattevi
Over time, organisms have evolved strategies to cope with the abundance of dioxygen on Earth. Oxygen-utilizing enzymes tightly control the reactions involving O2 mostly by modulating the reactivity of their cofactors. Flavins are extremely versatile cofactors that are capable of undergoing redox reactions by accepting either one electron or two electrons, alternating between the oxidized and the reduced states. The physical and chemical principles of flavin-based chemistry have been investigated widely. In the following pages we summarize the state of the art on a key area of research in flavin enzymology: the molecular basis for the activation of O2 by flavin-dependent oxidases and monooxygenases...
January 11, 2018: Chemical Reviews
Wei Chen, Mingbo Qu, Yong Zhou, Qing Yang
Chitin is a linear homopolymer of N-acetyl-β-D-glucosamines and a major structural component of insect cuticles. Chitin hydrolysis involves glycoside hydrolase family 18 (GH18) chitinases. In insects, chitin hydrolysis is essential for periodic shedding of the old cuticle ecdysis and proceeds via a pathway different from that in the well-studied bacterial chitinolytic system. Group II chitinase (ChtII) is a widespread chitinolytic enzyme in insects and contains the greatest number of catalytic domains and chitin binding domains among chitinases...
January 9, 2018: Journal of Biological Chemistry
Justin B Schaal, Thorsten Maretzky, Dat Q Tran, Patti A Tran, Prasad Tongaonkar, Carl P Blobel, André J Ouellette, Michael E Selsted
Theta-defensins (θ-defensins) are macrocyclic peptides expressed exclusively in granulocytes and selected epithelia of Old World monkeys.  They contribute to anti-pathogen host defense responses by directly killing a diverse range of microbes.  Of note, θ-defensins also modulate microbe-induced inflammation by affecting the production of soluble tumor necrosis factor (sTNF) and other proinflammatory cytokines.  Here, we report that natural rhesus macaque θ-defensin (RTD) isoforms regulate sTNF cellular release by inhibiting TNF alpha converting enzyme (TACE; also known as a disintegrin and metalloprotease 17; ADAM17), the primary pro-TNF sheddase...
January 9, 2018: Journal of Biological Chemistry
Atsuhiko Ishida, Noriyuki Sueyoshi, Isamu Kameshita
Intracellular signal transduction is built on the basis of the subtle balance between phosphorylation and dephosphorylation. Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F/POPX2) and CaMKP-N (PPM1E/POPX1) are Ser/Thr phosphatases that belong to the PPM (protein phosphatase, Mg2+/Mn2+-dependent) family. The former was discovered in rat brain as a novel protein phosphatase regulating Ca2+/calmodulin-dependent protein kinases (CaMKs), whereas the latter was first identified in human cDNA databases using the rat CaMKP sequence...
January 6, 2018: Archives of Biochemistry and Biophysics
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"