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Enzymology

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https://www.readbyqxmd.com/read/29323892/same-substrate-many-reactions-oxygen-activation-in-flavoenzymes
#1
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
https://www.readbyqxmd.com/read/29317504/structural-analysis-of-group-ii-chitinase-chtii-catalysis-completes-the-puzzle-of-chitin-hydrolysis-in-insects
#2
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
https://www.readbyqxmd.com/read/29317500/macrocyclic-%C3%AE-defensins-suppress-tumor-necrosis-factor-%C3%AE-tnf-%C3%AE-shedding-by-inhibition-of-tnf-%C3%AE-converting-enzyme
#3
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
https://www.readbyqxmd.com/read/29317228/functions-and-dysfunctions-of-ca2-calmodulin-dependent-protein-kinase-phosphatase-camkp-ppm1f-and-camkp-n-ppm1e
#4
REVIEW
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
https://www.readbyqxmd.com/read/29302039/targeting-the-corest-complex-with-dual-histone-deacetylase-and-demethylase-inhibitors
#5
Jay H Kalin, Muzhou Wu, Andrea V Gomez, Yun Song, Jayanta Das, Dawn Hayward, Nkosi Adejola, Mingxuan Wu, Izabela Panova, Hye Jin Chung, Edward Kim, Holly J Roberts, Justin M Roberts, Polina Prusevich, Jeliazko R Jeliazkov, Shourya S Roy Burman, Louise Fairall, Charles Milano, Abdulkerim Eroglu, Charlotte M Proby, Albena T Dinkova-Kostova, Wayne W Hancock, Jeffrey J Gray, James E Bradner, Sergio Valente, Antonello Mai, Nicole M Anders, Michelle A Rudek, Yong Hu, Byungwoo Ryu, John W R Schwabe, Andrea Mattevi, Rhoda M Alani, Philip A Cole
Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entinostat. Cell-based experiments demonstrate that corin exhibits a superior anti-proliferative profile against several melanoma lines and cutaneous squamous cell carcinoma lines compared to its parent monofunctional inhibitors but is less toxic to melanocytes and keratinocytes...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29242615/mechanistic-enzymology-in-drug-discovery-a-fresh-perspective
#6
Geoffrey A Holdgate, Thomas D Meek, Rachel L Grimley
This corrects the article DOI: 10.1038/nrd.2017.219.
December 15, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29236385/lipoxygenases-and-their-metabolites-in-formation-of-plant-stress-tolerance
#7
L M Babenko, M M Shcherbatiuk, T D Skaterna, I V Kosakivska
The review focuses on the analysis of new information concerning molecular enzymology of lipoxygenases – proteins involved in lipid peroxidation and found in animals and plants. Modern concept of structural features, catalytic characteristics and functions of lipoxygenase family enzymes as well as products of their catalytic activity in plants have been discussed and summarized. Issues of enzyme localization in plant cells and tissues, evolution and distribution of lipoxygenases, involvement in production of signaling substances involved in formation of adaptation response to abiotic and biotic stress factors and in regulation of lipoxygenase signal system activity are highlighted...
January 2017: Ukrainian Biochemical Journal
https://www.readbyqxmd.com/read/29233225/photosynthetic-water-splitting-by-the-mn4ca2-ox-catalyst-of-photosystem-ii-its-structure-robustness-and-mechanism
#8
James Barber
The biological energy cycle of our planet is driven by photosynthesis whereby sunlight is absorbed by chlorophyll and other accessory pigments. The excitation energy is then efficiently transferred to a reaction centre where charge separation occurs in a few picoseconds. In the case of photosystem II (PSII), the energy of the charge transfer state is used to split water into oxygen and reducing equivalents. This is accomplished by the relatively low energy content of four photons of visible light. PSII is a large multi-subunit membrane protein complex embedded in the lipid environment of the thylakoid membranes of plants, algae and cyanobacteria...
January 2017: Quarterly Reviews of Biophysics
https://www.readbyqxmd.com/read/29228335/gram-scale-production-of-recombinant-microbial-enzymes-in-shake-flasks
#9
Lukas Chrast, Radka Chaloupkova, Jiri Damborsky
Heterologous production of recombinant proteins is a cornerstone of microbiological and biochemical research as well as various biotechnological processes. Yields and quality of produced proteins have a tremendous impact on structural and enzymology studies, development of new biopharmaceuticals and establishing new biocatalytic processes. Majority of current protocols for recombinant protein expression in Escherichia coli exploit batch cultures with complex media, often providing low yields of the target protein due to oxygen transfer limitation, rapid depletion of carbon sources, and pH changes during the cultivation...
December 5, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29226071/structural-enzymology-comparisons-of-multifunctional-enzyme-type-1-mfe1-the-flexibility-of-its-dehydrogenase-part
#10
Prasad Kasaragod, Getnet B Midekessa, Shruthi Sridhar, Werner Schmitz, Tiila-Riikka Kiema, Jukka K Hiltunen, Rik K Wierenga
Multifunctional enzyme, type-1 (MFE1) is a monomeric enzyme with a 2E-enoyl-CoA hydratase and a 3S-hydroxyacyl-CoA dehydrogenase (HAD) active site. Enzyme kinetic data of rat peroxisomal MFE1 show that the catalytic efficiencies for converting the short-chain substrate 2E-butenoyl-CoA into acetoacetyl-CoA are much lower when compared with those of the homologous monofunctional enzymes. The mode of binding of acetoacetyl-CoA (to the hydratase active site) and the very similar mode of binding of NAD + and NADH (to the HAD part) are described and compared with those of their monofunctional counterparts...
December 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29223926/an-update-on-factor-xi-structure-and-function
#11
REVIEW
Bassem M Mohammed, Anton Matafonov, Ivan Ivanov, Mao-Fu Sun, Qiufang Cheng, S Kent Dickeson, Chan Li, David Sun, Ingrid M Verhamme, Jonas Emsley, David Gailani
Factor XI (FXI) is the zymogen of a plasma protease, factor XIa (FXIa), that contributes to thrombin generation during blood coagulation by proteolytic activation of several coagulation factors, most notably factor IX (FIX). FXI is a homolog of prekallikrein (PK), a component of the plasma kallikrein-kinin system. While sharing structural and functional features with PK, FXI has undergone adaptive changes that allow it to contribute to blood coagulation. Here we review current understanding of the biology and enzymology of FXI, with an emphasis on structural features of the protein as they relate to protease function...
January 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29192286/mechanistic-enzymology-in-drug-discovery-a-fresh-perspective
#12
REVIEW
Geoffrey A Holdgate, Thomas D Meek, Rachel L Grimley
Given the therapeutic and commercial success of small-molecule enzyme inhibitors, as exemplified by kinase inhibitors in oncology, a major focus of current drug-discovery and development efforts is on enzyme targets. Understanding the course of an enzyme-catalysed reaction can help to conceptualize different types of inhibitor and to inform the design of screens to identify desired mechanisms. Exploiting this information allows the thorough evaluation of diverse compounds, providing the knowledge required to efficiently optimize leads towards differentiated candidate drugs...
December 1, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29180239/comparative-biochemistry-of-cytochrome-c-oxidase-in-animals
#13
A G Little, G Lau, K Mathers, S C Leary, C D Moyes
Cytochrome c oxidase (COX), the terminal enzyme of the electron transport system, is central to aerobic metabolism of animals. Many aspects of its structure and function are highly conserved, yet, paradoxically, it is also an important model for studying the evolution of the metabolic phenotype. In this review, part of a special issue honouring Peter Hochachka, we consider the biology of COX from the perspective of comparative and evolutionary biochemistry. The approach is to consider what is known about the enzyme in the context of conventional biochemistry, but focus on how evolutionary researchers have used this background to explore the role of the enzyme in biochemical adaptation of animals...
November 25, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29165235/synthesis-of-n-acetyl-d-quinovosamine-in-rhizobium-etli-ce3-is-completed-after-its-4-keto-precursor-is-linked-to-a-carrier-lipid
#14
Tiezheng Li, K Dale Noel
Bacterial O-antigens are synthesized on lipid carriers before being transferred to lipopolysaccharide core structures. Rhizobium etli CE3 lipopolysaccharide is a model for understanding O-antigen biological function. CE3 O-antigen structure and genetics are known. However, proposed enzymology for CE3 O-antigen synthesis has been examined very little in vitro, and even the sugar added to begin the synthesis is uncertain. A model based on mutagenesis studies predicts that 2-acetamido-2,6-dideoxy-d-glucose (QuiNAc) is the first O-antigen sugar and that genes wreV, wreQ and wreU direct QuiNAc synthesis and O-antigen initiation...
November 22, 2017: Microbiology
https://www.readbyqxmd.com/read/29161251/enzymology-i-want-my-cluster-back
#15
Caitlin Deane
No abstract text is available yet for this article.
November 21, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29148757/cross-linked-artificial-enzyme-crystals-as-heterogeneous-catalysts-for-oxidation-reactions
#16
Sarah Lopez, Laurianne Rondot, Chloé Leprêtre, Caroline Marchi-Delapierre, Stéphane Ménage, Christine Cavazza
Designing systems that merge the advantages of heterogeneous catalysis, enzymology and molecular catalysis represents the next major goal for sustainable chemistry. Cross-linked enzyme crystals display most of these essential assets (well-designed mesoporous support, protein selectivity, molecular recognition of substrates). Nevertheless, a lack of reaction diversity, particularly in the field of oxidation, remains a constraint for their increased use in the field. Here, thanks to the design of cross-linked artificial non-heme iron oxygenase crystals, we filled this gap by developing bio-based heterogeneous catalysts capable of oxidizing carbon-carbon double bonds...
November 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29143132/thermostable-and-highly-specific-l-aspartate-oxidase-from-thermococcus-litoralis-dsm-5473-cloning-overexpression-and-enzymological-properties
#17
Tsubasa Washio, Tadao Oikawa
We successfully expressed the L-aspartate oxidase homolog gene (accession no: OCC_06611) of Thermococcus litoralis DSM 5473 in the soluble fraction of Escherichia coli BL21 (DE3) using a pET21b vector with 6X His tag at its C-terminus. The gene product (Tl-LASPO) showed L-aspartate oxidase activity in the presence of FAD in vitro, and this report is the first that details an L-aspartate oxidase derived from a Thermococcus species. The homologs of Tl-LASPO existed mainly in archaea, especially in the genus of Thermococcus, Pyrococcus, Sulfolobus, and Halobacteria...
November 15, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/29138240/kinetics-of-h2o2-driven-degradation-of-chitin-by-a-bacterial-lytic-polysaccharide-monooxygenase
#18
Silja Kuusk, Bastien Bissaro, Piret Kuusk, Zarah Forsberg, Vincent G H Eijsink, Morten Sørlie, Priit Väljamäe
Lytic polysaccharide monooxygenases (LPMOs) catalyze the oxidative cleavage of glycosidic bonds in recalcitrant polysaccharides, such as cellulose and chitin, and are of interest in biotechnological utilization of these abundant biomaterials. It has recently been shown that LPMOs can use H2O2, instead of O2, as a co-substrate. This peroxygenase-like reaction by a mono-copper enzyme is unprecedented in nature and opens new avenues in chemistry and enzymology. Here, we provide the first detailed kinetic characterization of chitin degradation by the bacterial LPMO chitin-binding protein CBP21 using H2O2 as co-substrate...
November 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29123679/mix-and-diffuse-serial-synchrotron-crystallography
#19
Kenneth R Beyerlein, Dennis Dierksmeyer, Valerio Mariani, Manuela Kuhn, Iosifina Sarrou, Angelica Ottaviano, Salah Awel, Juraj Knoska, Silje Fuglerud, Olof Jönsson, Stephan Stern, Max O Wiedorn, Oleksandr Yefanov, Luigi Adriano, Richard Bean, Anja Burkhardt, Pontus Fischer, Michael Heymann, Daniel A Horke, Katharina E J Jungnickel, Elena Kovaleva, Olga Lorbeer, Markus Metz, Jan Meyer, Andrew Morgan, Kanupriya Pande, Saravanan Panneerselvam, Carolin Seuring, Aleksandra Tolstikova, Julia Lieske, Steve Aplin, Manfred Roessle, Thomas A White, Henry N Chapman, Alke Meents, Dominik Oberthuer
Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers...
November 1, 2017: IUCrJ
https://www.readbyqxmd.com/read/29120187/mechanism-of-competitive-inhibition-and-destabilization-of-acidothermus-cellulolyticus-endoglucanase-1-by-ionic-liquids
#20
Samantha R Summers, K G Sprenger, Jim Pfaendtner, Jan Marchant, Michael F Summers, Joel L Kaar
The ability of ionic liquids (ILs) to solubilize cellulose has sparked interest in their use for enzymatic biomass processing. However, this potential is yet to be realized, primarily because ILs inactivate requisite cellulases by mechanisms that are yet to be identified. We used a combination of enzymology, circular dichroism (CD), nuclear magnetic resonance (NMR), and molecular dynamics (MD) methods to investigate the molecular basis for the inactivation of the endocellulase 1 (E1) from Acidothermus cellulolyticus by the imidazolium IL 1-butyl-3-methylimidazolium chloride ([BMIM][Cl])...
November 21, 2017: Journal of Physical Chemistry. B
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