- Drugs and Lactation Database (LactMed): Furosemide [BOOK]Drugs and Lactation Database (LactMed). National Library of Medicine (US): Bethesda (MD)BOOK
- Because little information is available on the use of furosemide during breastfeeding and because intense diuresis from high doses might decrease lactation, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Low doses of furosemide (20 mg daily) do not suppress lactation.
- Structure and Function of a Dual Reductase-Dehydratase Enzyme System Involved in p-Terphenyl Biosynthesis. [Journal Article]
- We report the identification of the ter gene cluster responsible for the formation of the p-terphenyl derivatives terfestatins B and C and echoside B from the Appalachian Streptomyces strain RM-5-8. We characterize the function of TerB/C, catalysts that work together as a dual enzyme system in the biosynthesis of natural terphenyls. TerB acts as a reductase and TerC as a dehydratase to enable the…
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- Differential lysine-mediated allosteric regulation of plant dihydrodipicolinate synthase isoforms. [Journal Article]
- Lysine biosynthesis in plants occurs via the diaminopimelate pathway. The first committed and rate-limiting step of this pathway is catalysed by dihydrodipicolinate synthase (DHDPS), which is allosterically regulated by the end product, l-lysine (lysine). Given that lysine is a common nutritionally limiting amino acid in cereal crops, there has been much interest in probing the regulation of DHDP…
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- Metal chaperone, NhpC, involved in the metallocenter biosynthesis of nitrile hydratase. [Journal Article]
- Pseudomonas chlororaphis B23 yields nitrile hydratase (NHase) used for the production of 5-cyanovaleramide at the industrial level. Although the nhpC gene (known as P47K) located just downstream of the NHase structural genes (nhpAB) has been important for efficient NHase expression, the key role of nhpC remains poorly studied. Here, we purified two NHases expressed in the presence and absence of …
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- The Fe-type nitrile hydratase from Rhodococcus equi TG328-2 forms an alpha-activator protein complex. [Journal Article]
- An Fe-type nitrile hydratase α(ɛ) protein complex from Rhodococcus equi TG328-2 (ReNHase) was discovered and shown by MALDI-TOF to form a 1:1 complex. As isolated, the α(ɛ) protein complex exhibited no detectable NHase activity even in the presence of iron. The addition of the ReNHase β-subunit and Fe(II) to the ReNHase apo-α(ε) complex, provided an enzyme with a kcat value of 0.7 ± 0.1 s-1 using…
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- Drugs and Lactation Database (LactMed): Hydrochlorothiazide [BOOK]Drugs and Lactation Database (LactMed). National Library of Medicine (US): Bethesda (MD)BOOK
- Hydrochlorothiazide doses of 50 mg daily or less are acceptable during lactation. Intense diuresis with large doses may decrease breastmilk production.
- Substrate Locking Promotes Dimer-Dimer Docking of an Enzyme Antibiotic Target. [Journal Article]
- Protein dynamics manifested through structural flexibility play a central role in the function of biological molecules. Here we explore the substrate-mediated change in protein flexibility of an antibiotic target enzyme, Clostridium botulinum dihydrodipicolinate synthase. We demonstrate that the substrate, pyruvate, stabilizes the more active dimer-of-dimers or tetrameric form. Surprisingly, ther…
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- Crystal structure of oleate hydratase from Stenotrophomonas sp. KCTC 12332 reveals conformational plasticity surrounding the FAD binding site. [Journal Article]
- Unsaturated fatty acids are toxic to various bacteria, causing their death or growth inhibition. To prevent this toxicity, unsaturated fatty acids should be converted into saturated fatty acids via hydrogenation reaction, which is the complete reduction of double bonds on the carbon chain. In a recent report, we observed that Stenotrophomonas sp. KCTC 12332 exhibited a high biotransformation acti…
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- A Review About Lycopene-Induced Nuclear Hormone Receptor Signalling in Inflammation and Lipid Metabolism via still Unknown Endogenous Apo-10´-Lycopenoids. [Journal Article]
- Lycopene is the red pigment in tomatoes and tomato products and is an important dietary carotenoid found in the human organism. Lycopene-isomers, oxidative lycopene metabolites and apo-lycopenoids are found in the food matrix. Lycopene intake derived from tomato consumption is associated with alteration of lipid metabolism and a lower incidence of cardiovascular diseases (CVD). Lycopene is mainly…
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- Identifying the Protein Interactions of the Cytosolic Iron-Sulfur Cluster Targeting Complex Essential for Its Assembly and Recognition of Apo-Targets. [Journal Article]
- The cytosolic iron-sulfur cluster assembly (CIA) system assembles iron-sulfur (FeS) cluster cofactors and inserts them into >20 apoprotein targets residing in the cytosol and nucleus. Three CIA proteins, called Cia1, Cia2, and Met18 in yeast, form the targeting complex responsible for apo-target recognition. There is little information about the structure of this complex or its mechanism of CIA s…
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- Insights into Substrate Modification by Dehydratases from Type I Polyketide Synthases. [Journal Article]
- Dehydration reactions play a crucial role in the de novo biosynthesis of fatty acids and a wide range of pharmacologically active polyketide natural products with strong emphasis on human medicine. The type I polyketide synthase PpsC from Mycobacterium tuberculosis catalyzes key biosynthetic steps of lipid virulence factors phthiocerol dimycocerosates and phenolic glycolipids. Given the insolubil…
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- The Structure of LiuC, a 3-Hydroxy-3-Methylglutaconyl CoA Dehydratase Involved in Isovaleryl-CoA Biosynthesis in Myxococcus xanthus, Reveals Insights into Specificity and Catalysis. [Journal Article]
- Myxobacteria are able to produce the important metabolite isovaleryl coenzyme A by a route other than leucine degradation. The first step into this pathway is mediated by LiuC, a member of the 3-methylglutaconyl CoA hydratases (MGCH). Here we present crystal structures refined to 2.05 and 1.1 Å of LiuC in the apo form and bound to coenzyme A, respectively. By using simulated annealing we modeled …
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- Biochemistry and Crystal Structure of Ectoine Synthase: A Metal-Containing Member of the Cupin Superfamily. [Journal Article]
- Ectoine is a compatible solute and chemical chaperone widely used by members of the Bacteria and a few Archaea to fend-off the detrimental effects of high external osmolarity on cellular physiology and growth. Ectoine synthase (EctC) catalyzes the last step in ectoine production and mediates the ring closure of the substrate N-gamma-acetyl-L-2,4-diaminobutyric acid through a water elimination rea…
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- Terminalia arjuna bark extract improves diuresis and attenuates acute hypobaric hypoxia induced cerebral vascular leakage. [Journal Article]
- CONCLUSIONS: Results of the present study indicate towards diuretic potential of hydro-alcoholic extract of T. arjuna bark and provide evidence for its novel application as a prophylactic to attenuate acute hypobaric hypoxia induced cerebral vascular leakage through ANP mediated modulation of renin-angiotensin-aldosterone system.
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- Structure and functional characterization of a bile acid 7α dehydratase BaiE in secondary bile acid synthesis. [Journal Article]
- Conversion of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) to the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) is performed by a few species of intestinal bacteria in the genus Clostridium through a multistep biochemical pathway that removes a 7α-hydroxyl group. The rate-determining enzyme in this pathway is bile acid 7α-dehydratase (baiE). In…
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- Crystal structure analysis of a fatty acid double-bond hydratase from Lactobacillus acidophilus. [Journal Article]
- Bacteria have evolved mechanisms for the hydrogenation of unsaturated fatty acids. Hydroxy fatty acid formation may be the first step in such a process; however, knowledge of the structural and mechanistic aspects of this reaction is scarce. Recently, myosin cross-reactive antigen was shown to be a bacterial FAD-containing hydratase which acts on the 9Z and 12Z double bonds of C16 and C18 non-est…
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- Crystal structure of type I 3-dehydroquinate dehydratase of Aquifex aeolicus suggests closing of active site flap is not essential for enzyme action. [Journal Article]
- Structural analyses of enzymes involved in biosynthetic pathways that are present in micro-organisms, but absent from mammals (for example Shikimate pathway) are important in developing anti-microbial drugs. Crystal structure of the Shikimate pathway enzyme, type I 3-dehydroquinate dehydratase (3-DHQase) from the hyperthermophilic bacterium Aquifex aeolicus was solved both as an apo form and in c…
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- Modeling holo-ACP:DH and holo-ACP:KR complexes of modular polyketide synthases: a docking and molecular dynamics study. [Journal Article]
- CONCLUSIONS: We have modeled the holo-ACP:DH and holo-ACP:KR complexes and identified the specific residues on DH and KR domains which are involved in interaction with ACP, phosphopantetheine and substrate moiety. Analysis of the conservation profile of binding pocket residues in homologous sequences of DH and KR domains indicated that, these results can also be extrapolated to reductive domains of other modular PKS clusters.
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- Unique biogenesis of high-molecular mass multimeric metalloenzyme nitrile hydratase: intermediates and a proposed mechanism for self-subunit swapping maturation. [Journal Article]
- Rhodococcus rhodochrous J1 produces high- and low-molecular mass nitrile hydratases (H-NHase and L-NHase, respectively), depending on the inducer. The incorporation of cobalt into L-NHase has been found to depend on the α-subunit exchange between cobalt-free L-NHase (apo-L-NHase) and its cobalt-containing mediator, NhlAE (holo-NhlAE), this novel mode of post-translational maturation having been n…
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- Induction of DNA breakage in U937 cells by oxazaphosphorines. [Journal Article]Folia Biol (Krakow). 2010; 58(1-2):15-20.FB
- Oxazaphosphorines are a class of DNA alkylating agents. The aim of the present study was to compare the possible influence of three new generation oxazaphosphorines, D-17272 (mafosfamide cyclohexylamine salt), D-18864 (4-hydro-peroxy-cyclophosphamide), and D-19575 (glufosfamide, beta-D-glucose-isophosphoramide mustard) on DNA damage induction in the human histiocytic lymphoma U937 cells. The flow…
- The structure of dihydrodipicolinate reductase (DapB) from Mycobacterium tuberculosis in three crystal forms. [Journal Article]
- Dihydrodipicolinate reductase (DHDPR, DapB) is an enzyme that belongs to the L-lysine biosynthetic pathway. DHDPR reduces the alpha,beta-unsaturated cyclic imine 2,3-dihydrodipicolinic acid to yield the compound 2,3,4,5-tetrahydrodipicolinic acid in a pyridine nucleotide-dependent reaction. The substrate of this reaction is the unstable product of the preceding enzyme dihydrodipicolinate synthase…
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- Substrate-mediated stabilization of a tetrameric drug target reveals Achilles heel in anthrax. [Journal Article]
- Bacillus anthracis is a gram-positive spore-forming bacterium that causes anthrax. With the increased threat of anthrax in biowarfare, there is an urgent need to characterize new antimicrobial targets from B. anthracis. One such target is dihydrodipicolinate synthase (DHDPS), which catalyzes the committed step in the pathway yielding meso-diaminopimelate and lysine. In this study, we employed CD …
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- A 12-week worksite health promotion program reduces cardiovascular risk factors in male workers with the apolipoprotein E2 and apolipoprotein E3 genotypes, but not in apolipoprotein E4 genotype. [Journal Article]
- Worksite health promotion programs focusing on diet and lifestyle modification have been shown to improve health outcomes in workers. The purpose of this study was to investigate whether a 12-week worksite health promotion program shows different response of cardiovascular risk factors in subjects according to apolipoprotein E (Apo E) genotype and obesity level in 141 male Korean industrial worke…
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- Self-subunit swapping chaperone needed for the maturation of multimeric metalloenzyme nitrile hydratase by a subunit exchange mechanism also carries out the oxidation of the metal ligand cysteine residues and insertion of cobalt. [Journal Article]
- The incorporation of cobalt into low molecular mass nitrile hydratase (L-NHase) of Rhodococcus rhodochrous J1 has been found to depend on the alpha-subunit exchange between cobalt-free L-NHase (apo-L-NHase lacking oxidized cysteine residues) and its cobalt-containing mediator (holo-NhlAE containing Cys-SO(2)(-) and Cys-SO(-) metal ligands), this novel mode of post-translational maturation having …
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- Structure and Function of [NiFe]-Hydrogenases. [Journal Article]
- [NiFe(Se)]-hydrogenases are hetero-dimeric enzymes present in many microorganisms where they catalyze the oxidation of molecular hydrogen or the reduction of protons. Like the other two types of hydrogen-metabolizing enzymes, the [FeFe]- and [Fe]-hydrogenases, [NiFe]-hydrogenases have a Fe(CO)(x) unit in their active sites that is most likely involved in hydride binding. Because of their complexi…
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- Proof of function of a putative 3-hydroxyacyl-acyl carrier protein dehydratase from higher plants by mass spectrometry of product formation. [Journal Article]
- The predicted mature portion of a putative 3-hydroxyacyl-ACP dehydratase (DH) from Arabidopsis was linked to an N-terminal poly-histidine-tag and the fusion protein expressed in Escherichia coli. Soluble dehydratase was present on induction at 25 degrees C and pure dehydratase eluted from a nickel-affinity column in 0.2-0.5M imidazole. High concentrations of imidazole were necessary to retain enz…
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- Discovery of posttranslational maturation by self-subunit swapping. [Journal Article]
- Several general mechanisms of metallocenter biosynthesis have been reported and reviewed, and in all cases, the components or subunits of an apoprotein remain in the final holoprotein. Here, we first discovered that one subunit of an apoenzyme did not remain in the functional holoenzyme. The cobalt-containing low-molecular-mass nitrile hydratase (L-NHase) of Rhodococcus rhodochrous J1 consists of…
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- Crystal structures of Toxoplasma gondii pterin-4a-carbinolamine dehydratase and comparisons with mammalian and parasite orthologues. [Journal Article]
- The enzyme pterin-4a-carbinolamine dehydratase (PCD) is important for the recycling of pterins within eukaryotic cells. A recombinant expression system for PCD from the apicomplexan parasite Toxoplasma gondii has been prepared, the protein purified and crystallised. Single crystal X-ray diffraction methods have produced a high-resolution structure (1.6A) of the apo-enzyme and a low-resolution str…
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- Structure and mechanism of HpcG, a hydratase in the homoprotocatechuate degradation pathway of Escherichia coli. [Journal Article]
- HpcG catalyses the hydration of a carbon-carbon double bond without the aid of any cofactor other than a simple divalent metal ion such as Mg(2+). Since the substrate has a nearby carbonyl group, it is believed that it first isomerises to form a pair of conjugated double bonds in the enol tautomer before Michael addition of water. Previous chemical studies of the reaction, and that of the related…
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- Structure of thiocyanate hydrolase: a new nitrile hydratase family protein with a novel five-coordinate cobalt(III) center. [Journal Article]
- Thiocyanate hydrolase (SCNase) of Thiobacillus thioparus THI115 is a cobalt(III)-containing enzyme catalyzing the degradation of thiocyanate to carbonyl sulfide and ammonia. We determined the crystal structures of the apo- and native SCNases at a resolution of 2.0 A. SCNases in both forms had a conserved hetero-dodecameric structure, (alphabetagamma)(4). Four alphabetagamma hetero-trimers were st…
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