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Enzymology

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https://www.readbyqxmd.com/read/28720496/substrate-binding-interferes-with-active-site-conformational-dynamics-in-endoglucanase-cel5a-from-thermobifida-fusca
#1
Xukai Jiang, Yuying Wang, Limei Xu, Guanjun Chen, Lushan Wang
The role of protein dynamics in enzyme catalysis is one of the most active areas in current enzymological research. Here, using endoglucanase Cel5A from Thermobifida fusca (TfCel5A) as a model, we applied molecular dynamics simulations to explore the dynamic behavior of the enzyme upon substrate binding. The collective motions of the active site revealed that the mechanism of TfCel5A substrate binding can likely be described by the conformational-selection model; however, we observed that the conformations of active site residues changed differently along with substrate binding...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#2
Hailong Shi, Yaya Cui, Yifei Qin
Serotonin (5-HT) is an important neurotransmitter and paracrine signaling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPH1 and TPH2 are the rate-limiting enzymes in the 5-HT biosynthesis process. TPH1 expression is mainly limited in the enterochromaffin cells and distributed in peripheries such as the skin and gut, while TPH2 is the predominant isoform in the CNS. In this study, mol002291 was screened as a drug-like compound from the TCM database for the inhibitor of TPH...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28699750/chemistry-and-enzymology-of-disulfide-cross-linking-in-proteins
#3
Deborah Fass, Colin Thorpe
Cysteine thiols are among the most reactive functional groups in proteins, and their pairing in disulfide linkages is a common post-translational modification in proteins entering the secretory pathway. This modest amino acid alteration, the mere removal of a pair of hydrogen atoms from juxtaposed cysteine residues, contrasts with the substantial changes that characterize most other post-translational reactions. However, the wide variety of proteins that contain disulfides, the profound impact of cross-linking on the behavior of the protein polymer, the numerous and diverse players in intracellular pathways for disulfide formation, and the distinct biological settings in which disulfide bond formation can take place belie the simplicity of the process...
July 12, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28691704/the-self-inhibitory-nature-of-metabolic-networks-and-its-alleviation-through-compartmentalization
#4
Mohammad Tauqeer Alam, Viridiana Olin-Sandoval, Anna Stincone, Markus A Keller, Aleksej Zelezniak, Ben F Luisi, Markus Ralser
Metabolites can inhibit the enzymes that generate them. To explore the general nature of metabolic self-inhibition, we surveyed enzymological data accrued from a century of experimentation and generated a genome-scale enzyme-inhibition network. Enzyme inhibition is often driven by essential metabolites, affects the majority of biochemical processes, and is executed by a structured network whose topological organization is reflecting chemical similarities that exist between metabolites. Most inhibitory interactions are competitive, emerge in the close neighbourhood of the inhibited enzymes, and result from structural similarities between substrate and inhibitors...
July 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28688251/site-selective-covalent-reactions-on-proteinogenic-amino-acids
#5
REVIEW
Wing Ho So, Yu Zhang, Wei Kang, Clarence T T Wong, Hongyan Sun, Jiang Xia
To achieve precise control of the signaling events or to achieve unmistakable synthesis of biomolecules, nature has evolved organic reactions involving proteinogenic amino acids with unparalleled site selectivity. For example, dedicated enzymes accurately dictate the site of post-translational modifications in signaling proteins, and ribosomes precisely link the C-terminal carboxylic acid of one unprotected amino acid with the N-terminal amino group of the other amino acid through spatially confined proximity...
July 5, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28683918/enzymology-of-microbial-dimethylsulfoniopropionate-catabolism
#6
Mishtu Dey
The biochemistry of dimethylsulfoniopropionate (DMSP) catabolism is reviewed. The microbes that catalyze the reactions central to DMSP catabolic pathways are described, and the focus is on the enzymology of the process. Approximately 10(9)tons of DMSP is released annually by marine eukaryotes as an osmolyte. A vast majority of DMSP is assimilated by bacteria through either a demethylation or lyase pathways, producing either the methane thiol or the volatile dimethylsulfide (DMS), respectively. Enzymatic breakdown of DMSP generates ~10(7)tons of DMS annually, which may have impact on global climate...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28652025/multiple-functionalities-of-reduced-flavin-in-the-non-redox-reaction-catalyzed-by-udp-galactopyranose-mutase
#7
REVIEW
Pablo Sobrado, John J Tanner
Flavin cofactors are widely used by enzymes to catalyze a broad range of chemical reactions. Traditionally, flavins in enzymes are regarded as redox centers, which enable enzymes to catalyze the oxidation or reduction of substrates. However, a new class of flavoenzyme has emerged over the past quarter century in which the flavin functions as a catalytic center in a non-redox reaction. Here we introduce the unifying concept of flavin hot spots to understand and categorize the mechanisms and reactivities of both traditional and noncanonical flavoenzymes...
June 24, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28644411/on-the-reaction-of-carbonyl-diphosphonic-acid-with-hydroxylamine-and-o-alkylhydroxylamines-unexpected-degradation-of-p-c-p-bridge
#8
Olga A Khomich, Dmitry V Yanvarev, Roman A Novikov, Alexey B Kornev, Elina Puljulla, Jouko Vepsäläinen, Alex R Khomutov, Sergey N Kochetkov
Derivatives of methylenediphosphonic acid possess wide spectra of biological activities and are used in enzymology as research tools as well as in practical medicine. Carbonyl diphosphonic acid is a promising starting building block for synthesis of functionally substituted methylenediphosphonates. Investigation of the interaction of carbonyl diphosphonic acid with hydroxylamine clearly demonstrates that it is impossible to isolate oxime within the pH range 2-12, while only cyanophosphonic and phosphoric acids are the products of the fast proceeding Beckmann-like fragmentation...
June 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28631282/biosynthesis-of-complex-indole-alkaloids-elucidation-of-the-concise-pathway-of-okaramines
#9
Chen-Yu Lai, I-Wen Lo, Ranuka T Hewage, Yi-Chen Chen, Chien-Ting Chen, Chi-Fang Lee, Steven Lin, Man-Cheng Tang, Hsiao-Ching Lin
The okaramines are a class of complex indole alkaloids isolated from Penicillium and Aspergillus species. Their potent insecticidal activity arises from selectively activating glutamate-gated chloride channels (GluCls) in invertebrates, not affecting human ligand-gated anion channels. Okaramines B (1) and D (2) contain a polycyclic skeleton, including an azocine ring and an unprecedented 2-dimethyl-3-methyl-azetidine ring. Owing to their complex scaffold, okaramines have inspired many total synthesis efforts, but the enzymology of the okaramine biosynthetic pathway remains unexplored...
June 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28630164/single-molecule-nanopore-enzymology
#10
REVIEW
Kherim Willems, Veerle Van Meervelt, Carsten Wloka, Giovanni Maglia
Biological nanopores are a class of membrane proteins that open nanoscale water conduits in biological membranes. When they are reconstituted in artificial membranes and a bias voltage is applied across the membrane, the ionic current passing through individual nanopores can be used to monitor chemical reactions, to recognize individual molecules and, of most interest, to sequence DNA. In addition, a more recent nanopore application is the analysis of single proteins and enzymes. Monitoring enzymatic reactions with nanopores, i...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28609756/realization-of-microbial-community-stratification-for-single-stage-nitrogen-removal-in-a-sequencing-batch-biofilter-granular-reactor
#11
Na Sun, Chenghao Ge, Hafiz Adeel Ahmad, Baoyu Gao, Shou-Qing Ni
A permanent microbial stratified nitrogen removal system coupling anammox with partial nitrification (SNAP) in a sequencing batch biofilter granular reactor (SBBGR) was successfully constructed for the treatment of ammonia-rich wastewater. With a nitrogen loading rate of 0.1kgNm(-3)·d(-1), the maximal ammonia and total nitrogen removal efficiencies could reach up to 96.08% and 84.86% on day 108, respectively. The pH, DO profiles revealed a switch of functional species (AOB and anammox) at a typical intermittent aeration cycle...
October 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28604895/simultaneous-enzymatic-activity-modulation-and-rapid-determination-of-enzyme-kinetics-by-highly-crystalline-graphite-dots
#12
Rui Shi, Hao Li, Enhui Wu, Lipeng Xiong, Rui Lv, Ruochen Guo, Yang Liu, Guoqiang Xu, Zhenhui Kang, Jian Liu
The research field in enzyme-based biotechnology urgently requires the discovery of new materials and methods with high-performance. Here we report that highly crystalline graphite dots (GDs) can modulate enzyme activities, and simultaneously allow for real-time measurements on enzyme kinetics in combination with mass spectrometry (MS). A well-defined modulation of lipolytic activities from inhibition to enhancement can be realized by selectively coupling lipase enzymes with GDs containing specific functional groups on the surface...
June 12, 2017: Nanoscale
https://www.readbyqxmd.com/read/28601227/trmd-a-methyl-transferase-for-trna-methylation-with-m-1-g37
#13
Ya-Ming Hou, Ryuma Matsubara, Ryuichi Takase, Isao Masuda, Joanna I Sulkowska
TrmD is an S-adenosyl methionine (AdoMet)-dependent methyl transferase that synthesizes the methylated m(1)G37 in tRNA. TrmD is specific to and essential for bacterial growth, and it is fundamentally distinct from its eukaryotic and archaeal counterpart Trm5. TrmD is unusual by using a topological protein knot to bind AdoMet. Despite its restricted mobility, the TrmD knot has complex dynamics necessary to transmit the signal of AdoMet binding to promote tRNA binding and methyl transfer. Mutations in the TrmD knot block this intramolecular signaling and decrease the synthesis of m(1)G37-tRNA, prompting ribosomes to +1-frameshifts and premature termination of protein synthesis...
2017: Enzymes
https://www.readbyqxmd.com/read/28581740/conformational-selection-as-the-mechanism-of-guest-binding-in-a-flexible-supramolecular-host
#14
Cynthia M Hong, David M Kaphan, Robert G Bergman, Kenneth N Raymond, F Dean Toste
This study offers a detailed mechanistic investigation of host-guest encapsulation behavior in a new enzyme-mimetic metal-ligand host and provides the first observation of a conformational selection mechanism (as opposed to induced fit) in a supramolecular system. The Ga4L4 host described features a C3-symmetric ligand motif with meta-substituted phenyl spacers, which enables the host to initially self-assemble into an S4-symmetric structure and then subsequently isomerize to a T-symmetric tetrahedron for better accommodation of a sufficiently large guest...
June 5, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28554725/substrate-inhibition-of-17beta-hsd1-in-living-cells-and-regulation-of-17beta-hsd7-by-17beta-hsd1-knockdown
#15
Hui Han, Jean-François Thériault, Guang Chen, Sheng-Xiang Lin
This study addresses first the role of human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) in breast cancer (BC). The enzyme has a high estrone-activating activity that is subject to strong substrate inhibition as shown by enzyme kinetics at the molecular level. We used BC cells to verify this phenomenon in living cells: estrone concentration increase did reduce the reaction with 0.025 to 4μM substrate. Moreover, 5α-dihydrotestosterone (DHT) demonstrated some inhibition of estrogen activation at both the molecular and cellular level...
May 26, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28546645/fluorination-at-the-4-position-alters-the-substrate-behavior-of-l-glutamine-and-l-glutamate-implications-for-positron-emission-tomography-of-neoplasias
#16
Thomas M Jeitner, Eva Kristoferson, Juan A Azcona, John T Pinto, Clint Stalnecker, Jon W Erickson, Hank F Kung, Jianyong Li, Karl Ploessl, Arthur J L Cooper
Two 4-fluoro-L-glutamine diastereoisomers [(2S,4R)-4-FGln, (2S,4S)-4-FGln] were previously developed for positron emission tomography. Label uptake into two tumor cell types was greater with [(18)F](2S,4R)-4-FGln than with [(18)F](2S,4S)-4-FGln. In the present work we investigated the enzymology of two diastereoisomers of 4-FGln, two diastereoisomers of 4-fluoroglutamate (4-FGlu) (potential metabolites of the 4-FGln diastereoisomers) and another fluoro-derivative of L-glutamine [(2S,4S)-4-(3-fluoropropyl)glutamine (FP-Gln)]...
December 2016: Journal of Fluorine Chemistry
https://www.readbyqxmd.com/read/28543031/in-memoriam-professor-jean-pierre-von-wartburg-1931-to-2017
#17
Helmut K Seitz
No abstract text is available yet for this article.
May 25, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28533982/lid-opening-and-conformational-stability-of-t1-lipase-is-mediated-by-increasing-chain-length-polar-solvents
#18
Jonathan Maiangwa, Mohd Shukuri Mohamad Ali, Abu Bakar Salleh, Raja Noor Zaliha Raja Abd Rahman, Yahaya M Normi, Fairolniza Mohd Shariff, Thean Chor Leow
The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD) of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol) and water mixture systems to a concentration of 50%...
2017: PeerJ
https://www.readbyqxmd.com/read/28529757/enzyme-activities-and-gene-expression-of-starch-metabolism-provide-insights-into-grape-berry-development
#19
Xudong Zhu, Chaobo Zhang, Weimin Wu, Xiaopeng Li, Chuan Zhang, Jinggui Fang
Grapes are categorized as a non-climacteric type of fruit which its ripening is not associated to important rises in respiration and ethylene synthesis. The starch metabolism shares a certain role in the carbohydrate metabolic pathways during grape berry development, and is regarded as an important transient pool in the pathway of sugar accumulation. However, the comprehensive role of starch and its contribution to the quality and flavor of grape berry have not been explored thoroughly. In this study, the expression levels of genes enzyme activities and carbohydrate concentrations related to starch metabolism, were analyzed to understand the molecular mechanism of starch accumulation during grape berry development...
2017: Horticulture Research
https://www.readbyqxmd.com/read/28526692/understanding-the-interrelationship-between-the-synthesis-of-urea-and-gluconeogenesis-by-formulating-an-overall-balanced-equation
#20
Piero L Ipata, Rossana Pesi
It is well known that a strong metabolic interrelationship exists between ureagenesis and gluconeogenesis. In this paper, we present a detailed, overall equation, describing a possible metabolic link between ureagenesis and gluconeogenesis. We adopted a guided approach in which we strongly suggest that students, when faced with the problem of obtaining the overall equation of a metabolic pathway, carefully account for all atoms and charges of the single reactions, as well as the cellular localizations of the substrates, and the related transport systems...
June 1, 2017: Advances in Physiology Education
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