Genomes and Genes
Summary: Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.
- Lu X, Pu C, Shi Q, Luo W, Li K. [GNE gene mutation analysis in 5 patients with distal myopathy with rimmed vacuoles]. Nan Fang Yi Ke Da Xue Xue Bao. 2011;31:1421-4 pubmed..To investigate GNE gene mutations in 5 Chinese patients with distal myopathy with rimmed vacuoles (DMRV)...
- Pearson D, Carell T. Assay of both activities of the bifunctional tRNA-modifying enzyme MnmC reveals a kinetic basis for selective full modification of cmnm5s2U to mnm5s2U. Nucleic Acids Res. 2011;39:4818-26 pubmed publisher..The assay method developed here represents a general approach for the comparative analysis of tRNA-modifying enzymes. ..
- Ramaswamy G, Sohn P, Eberhardt A, Serra R. Altered responsiveness to TGF-? results in reduced Papss2 expression and alterations in the biomechanical properties of mouse articular cartilage. Arthritis Res Ther. 2012;14:R49 pubmed publisher..TGF-? maintains biomechanical properties and regulates expression of Papss2 and sulfation of glycosaminoglycans in mouse articular cartilage. ..
- Milman Krentsis I, Sela I, Eiges R, Blanchard V, Berger M, Becker Cohen M, et al. GNE is involved in the early development of skeletal and cardiac muscle. PLoS ONE. 2011;6:e21389 pubmed publisher..These findings could open new avenues in the understanding of muscle function mechanisms in health and in disease. ..
- East J, Kennedy A, Tomsig J, De Leon A, Lynch K, Macdonald T. Synthesis and structure-activity relationships of tyrosine-based inhibitors of autotaxin (ATX). Bioorg Med Chem Lett. 2010;20:7132-6 pubmed publisher..Here we describe the SAR of ATX inhibitor, VPC8a202, and apply this SAR knowledge towards developing a high potency inhibitor. We found that electron density in the pyridine region greatly influences activity of our inhibitors at ATX. ..
- Venugopal A, Bryk R, Shi S, Rhee K, Rath P, Schnappinger D, et al. Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Cell Host Microbe. 2011;9:21-31 pubmed publisher..Mtb deficient in both DlaT and PdhC phenocopies Lpd-deficient Mtb. Thus, Mtb critically requires BCKADH along with PDH and PNR/P for pathogenesis. These findings position Lpd as a potential target for anti-infectives against Mtb. ..
- Han Y, Zhang M, Hong Y, Zhu Z, Li D, Li X, et al. Characterization of thioredoxin glutathione reductase in Schiotosoma japonicum. Parasitol Int. 2012;61:475-80 pubmed publisher..This study provides the basis for further investigations into the biological function of SjTGR and further evaluation of the potential use of this molecule as a vaccine candidate or new drug target is warranted...
- Manosas M, Spiering M, Ding F, Croquette V, Benkovic S. Collaborative coupling between polymerase and helicase for leading-strand synthesis. Nucleic Acids Res. 2012;40:6187-98 pubmed..The model quantitatively reproduces homologous and heterologous coupling results under various experimental conditions. ..
- Ghilarov D, Serebryakova M, Shkundina I, Severinov K. A major portion of DNA gyrase inhibitor microcin B17 undergoes an N,O-peptidyl shift during synthesis. J Biol Chem. 2011;286:26308-18 pubmed publisher..We speculate that the N,O-peptidyl shift undergone by Ser(52) is an intermediate of post-translational modification reactions catalyzed by the McbBCD synthase that normally lead to formation of McB heterocycles. ..
- Althoff T, Mills D, Popot J, Kuhlbrandt W. Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J. 2011;30:4652-64 pubmed publisher..The arrangement of respiratory chain complexes suggests two possible pathways for efficient electron transfer through the supercomplex, of which the shorter branch through the complex III monomer proximal to complex I may be preferred. ..
- Deng L, Diao J, Chen P, Pujari V, Yao Y, Cheng G, et al. Inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies. J Med Chem. 2011;54:4721-34 pubmed publisher..Overall, these results provide implications in the future design and development of potent DXR inhibitors. ..
- Górna M, Carpousis A, Luisi B. From conformational chaos to robust regulation: the structure and function of the multi-enzyme RNA degradosome. Q Rev Biophys. 2012;45:105-45 pubmed publisher..Parallels are drawn with analogous machinery in organisms from all life domains. Finally, we conjecture on roles of the degradosome as a regulatory hub for complex cellular processes. ..
- Cunliffe M. Correlating carbon monoxide oxidation with cox genes in the abundant Marine Roseobacter Clade. ISME J. 2011;5:685-91 pubmed publisher..Subsequent analyses of a subset of nine MRC strains revealed that only MRC strains with both coxL forms are able to oxidise CO. ..
- Fonknechten N, Chaussonnerie S, Tricot S, Lajus A, Andreesen J, Perchat N, et al. Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence. BMC Genomics. 2010;11:555 pubmed publisher..With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed...
- Naj A, Beecham G, Martin E, Gallins P, Powell E, Konidari I, et al. Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities. PLoS Genet. 2010;6:e1001130 pubmed publisher..This finding is noteworthy, as MTHFD1L may play a role in the generation of methionine from homocysteine and influence homocysteine-related pathways and as levels of homocysteine are a significant risk factor for LOAD development. ..
- Cavalli S, Houben A, Albers H, van Tilburg E, de Ru A, Aoki J, et al. Development of an activity-based probe for autotaxin. Chembiochem. 2010;11:2311-7 pubmed publisher..Our activity-based reporter will be useful for monitoring ATX activity in biological fluids and for inhibitor screening. ..
- Roux C, Demuth J, Dunman P. Characterization of components of the Staphylococcus aureus mRNA degradosome holoenzyme-like complex. J Bacteriol. 2011;193:5520-6 pubmed publisher..Results also revealed that the recently recognized RNase RnpA interacts with the S. aureus degradosome and that this interaction is conserved in other Gram-positive organisms. ..
- Sela I, Milman Krentsis I, Shlomai Z, Sadeh M, Dabby R, Argov Z, et al. The proteomic profile of hereditary inclusion body myopathy. PLoS ONE. 2011;6:e16334 pubmed publisher..Taken together, these findings indicate a possible novel function of GNE in the muscle filamentous apparatus that could be involved in the pathogenesis of HIBM. ..
- Zhang G, Liu J, Ding W. Decreased xylitol formation during xylose fermentation in Saccharomyces cerevisiae due to overexpression of water-forming NADH oxidase. Appl Environ Microbiol. 2012;78:1081-6 pubmed publisher..33% increase due to noxE overexpression. At the same time, the glycerol yield also was reduced by 53.85% on account of the decrease in the NADH pool caused by overexpression of noxE...
- Hardwick S, Chan V, Broadhurst R, Luisi B. An RNA degradosome assembly in Caulobacter crescentus. Nucleic Acids Res. 2011;39:1449-59 pubmed publisher..Finally, we observe that the abundance of RNase E varies through the cell cycle, with maxima at morphological differentiation and cell division. This variation may contribute to the program of gene expression during cell division...
- Lehnik Habrink M, Newman J, Rothe F, Solovyova A, Rodrigues C, Herzberg C, et al. RNase Y in Bacillus subtilis: a Natively disordered protein that is the functional equivalent of RNase E from Escherichia coli. J Bacteriol. 2011;193:5431-41 pubmed publisher..The results presented in this study provide novel evidence for the idea that RNase Y is the functional equivalent of RNase E, even though the two enzymes do not share any sequence similarity. ..
- Andaloussi M, Henriksson L, Wieckowska A, Lindh M, Björkelid C, Larsson A, et al. Design, synthesis, and X-ray crystallographic studies of ?-aryl substituted fosmidomycin analogues as inhibitors of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase. J Med Chem. 2011;54:4964-76 pubmed publisher
- van den Boom J, Heider D, Martin S, Pastore A, Mueller J. 3'-Phosphoadenosine 5'-phosphosulfate (PAPS) synthases, naturally fragile enzymes specifically stabilized by nucleotide binding. J Biol Chem. 2012;287:17645-55 pubmed publisher..Moreover, naturally occurring changes in APS concentrations may be sensed by changes in the conformation of PAPSS2. ..
- Kitamura A, Sengoku T, Nishimoto M, Yokoyama S, Bessho Y. Crystal structure of the bifunctional tRNA modification enzyme MnmC from Escherichia coli. Protein Sci. 2011;20:1105-13 pubmed publisher..These results suggest that, although the MnmC1 and MnmC2 domains are physically linked, they could catalyze the two consecutive reactions in a rather independent manner. ..
- Guevara Flores A, Pardo J, Rendón J. Hysteresis in thioredoxin-glutathione reductase (TGR) from the adult stage of the liver fluke Fasciola hepatica. Parasitol Int. 2011;60:156-60 pubmed publisher..et al. (2008) J Biol Chem 283: 17898] needs to be reevaluated. ..
- Huang H, Day L, Cass C, Ballou D, Williams C, Williams D. Investigations of the catalytic mechanism of thioredoxin glutathione reductase from Schistosoma mansoni. Biochemistry. 2011;50:5870-82 pubmed publisher..Our data show that Cys-520 and Cys-574 are not likely to be involved in the catalytic mechanism. ..
- Andaloussi M, Lindh M, Björkelid C, Suresh S, Wieckowska A, Iyer H, et al. Substitution of the phosphonic acid and hydroxamic acid functionalities of the DXR inhibitor FR900098: an attempt to improve the activity against Mycobacterium tuberculosis. Bioorg Med Chem Lett. 2011;21:5403-7 pubmed publisher..The best inhibitors provided IC(50) values in the micromolar range, with a best value of 41 ?M. ..
- Prévost K, Desnoyers G, Jacques J, Lavoie F, Massé E. Small RNA-induced mRNA degradation achieved through both translation block and activated cleavage. Genes Dev. 2011;25:385-96 pubmed publisher..Thus, beyond translation initiation block, sRNA-induced mRNA cleavage requires several unexpected steps, many of which are determined by structural features of the target mRNA. ..
- Georgescu R, Kurth I, O Donnell M. Single-molecule studies reveal the function of a third polymerase in the replisome. Nat Struct Mol Biol. 2011;19:113-6 pubmed publisher..Second, tripolymerase replisomes are much more processive than dipolymerase replisomes. These features account for the unexpected three-polymerase-structure of bacterial replisomes. ..
- Schröder E, Gebel L, Eremeev A, Morgner J, Grum D, Knauer S, et al. Human PAPS synthase isoforms are dynamically regulated enzymes with access to nucleus and cytoplasm. PLoS ONE. 2012;7:e29559 pubmed publisher..Collectively, we describe unusual localisation signals of both PAPS synthase isoforms, mobile enzymes capable of executing their function in the cytoplasm as well as in the nucleus. ..
- Mori Yoshimura M, Monma K, Suzuki N, Aoki M, Kumamoto T, Tanaka K, et al. Heterozygous UDP-GlcNAc 2-epimerase and N-acetylmannosamine kinase domain mutations in the GNE gene result in a less severe GNE myopathy phenotype compared to homozygous N-acetylmannosamine kinase domain mutations. J Neurol Sci. 2012;318:100-5 pubmed publisher..50%). Data were verified using medical records available from 17 outpatient participants. Homozygous KD/KD participants exhibited a more severe phenotype compared to heterozygous ED/KD participants. ..
- Perez Gil J, Calisto B, Behrendt C, Kurz T, Fita I, Rodríguez Concepción M. Crystal structure of Brucella abortus deoxyxylulose-5-phosphate reductoisomerase-like (DRL) enzyme involved in isoprenoid biosynthesis. J Biol Chem. 2012;287:15803-9 pubmed publisher..As a proof of concept, we identified two strong DXR inhibitors that have virtually no effect on DRL activity...
- Bauman A, Broers B, Kline C, Blackburn N. A copper-methionine interaction controls the pH-dependent activation of peptidylglycine monooxygenase. Biochemistry. 2011;50:10819-28 pubmed publisher..A model is presented in which H108 is protonated with a pK(a) of 4.6 to generate the inactive low-pH form with Cu(H) coordinated by M109, H107, and H172. ..
- Wang X, Wortham N, Liu R, Proud C. Identification of residues that underpin interactions within the eukaryotic initiation factor (eIF2) 2B complex. J Biol Chem. 2012;287:8263-74 pubmed publisher..Lastly, our data show that eIF2B? promotes the expression of eIF2B?, providing a mechanism for achieving correct stoichiometry of these eIF2B subunits in the cell. ..
- Li H, Chen Q, Liu F, Zhang X, Liu T, Li W, et al. Clinical and molecular genetic analysis in Chinese patients with distal myopathy with rimmed vacuoles. J Hum Genet. 2011;56:335-8 pubmed publisher..1523T>C (p.L508S) was 25% in the Chinese patients with DMRV. Our findings expand the genetic spectrum of DMRV and indicate that the common mutations of GNE gene in DMRV may be variable among different ethnic populations...
- Morris K, Cao F, Onagi H, Altamore T, Gamble A, Easton C. Prohormone-substrate peptide sequence recognition by peptidylglycine ?-amidating monooxygenase and its reflection in increased glycolate inhibitor potency. Bioorg Med Chem Lett. 2012;22:7015-8 pubmed publisher..However, this changes the binding mode from one that depends on peptide sequence recognition to another primarily determined by the phenylalanine moiety, for both the substrates and analogous glycolate inhibitors. ..
- Lajoie M, Gregg C, Mosberg J, Washington G, Church G. Manipulating replisome dynamics to enhance lambda Red-mediated multiplex genome engineering. Nucleic Acids Res. 2012;40:e170 pubmed publisher..These improvements will facilitate ambitious genome engineering projects by minimizing dependence on time-consuming clonal isolation and screening. ..
- Rudzka K, Moreno D, Eipper B, Mains R, Estrin D, Amzel L. Coordination of peroxide to the Cu(M) center of peptidylglycine ?-hydroxylating monooxygenase (PHM): structural and computational study. J Biol Inorg Chem. 2013;18:223-32 pubmed publisher..The geometry of the observed side-on coordinated peroxide ligand in L(3)Cu(M)(II)O(2) (2-) is in good agreement with the results of a hybrid quantum mechanical-molecular mechanical optimization of this species. ..
- Sharma H, Landau M, Vargo M, Spasov K, Anderson K. First three-dimensional structure of Toxoplasma gondii thymidylate synthase-dihydrofolate reductase: insights for catalysis, interdomain interactions, and substrate channeling. Biochemistry. 2013;52:7305-7317 pubmed publisher..Taken together, these structural and kinetic studies reveal unique, functional regions on the T. gondii TS-DHFR enzyme that may be targeted for inhibition, thus paving the way for designing species specific inhibitors. ..
- Long A, O Brien C, Malhotra K, Schwall C, Albert A, Watts A, et al. A detergent-free strategy for the reconstitution of active enzyme complexes from native biological membranes into nanoscale discs. BMC Biotechnol. 2013;13:41 pubmed publisher..This facile, single-step strategy obviates the requirement for detergents and yields membrane complexes suitable for structural and functional studies. ..
- Ge X, Shi X, Shi L, Liu J, Stone V, Kong F, et al. Involvement of NADH Oxidase in Biofilm Formation in Streptococcus sanguinis. PLoS ONE. 2016;11:e0151142 pubmed publisher..NADH oxidase-related metabolic pathways were analyzed, further clarifying the function of this enzyme in biofilm formation. ..
- Huuskonen P, Myllynen P, Storvik M, Pasanen M. The effects of aflatoxin B1 on transporters and steroid metabolizing enzymes in JEG-3 cells. Toxicol Lett. 2013;218:200-6 pubmed publisher..These alterations may lead to anomalies in the foetoplacental hormonal homeostasis...
- Chou Y, Jeng Y, Mao T. HSD3B1 is a specific trophoblast-associated marker not expressed in a wide spectrum of tumors. Int J Gynecol Cancer. 2013;23:343-7 pubmed publisher..Our study further confirmed that HSD3B1 is a highly specific trophoblast-associated marker that can be used in the distinction of trophoblastic tumorlike lesions and tumors from nontrophoblastic lesions and tumors. ..
- Vieux E, Wohlever M, Chen J, Sauer R, Baker T. Distinct quaternary structures of the AAA+ Lon protease control substrate degradation. Proc Natl Acad Sci U S A. 2013;110:E2002-8 pubmed publisher..Our results support a unique gating mechanism that allows the repertoire of Lon substrates to be tuned by its assembly state. ..
- Singh V, Ghosh I. Methylerythritol phosphate pathway to isoprenoids: kinetic modeling and in silico enzyme inhibitions in Plasmodium falciparum. FEBS Lett. 2013;587:2806-17 pubmed publisher..falciparum MEP pathway. These groups of targets can be exploited for independent anti-malarial drugs. ..
- Soriano E, Zhang Y, Colabroy K, Sanders J, Settembre E, Dorrestein P, et al. Active-site models for complexes of quinolinate synthase with substrates and intermediates. Acta Crystallogr D Biol Crystallogr. 2013;69:1685-96 pubmed publisher..2005), J. Biol. Chem. 280, 26645-26648]. The domain arrangement in P. furiosus QS may be related to protection of cysteine side chains, which are required to chelate the [4Fe-4S] cluster, prior to cluster assembly. ..
- Lapierre P, Beland K, Yang R, Alvarez F. Adoptive transfer of ex vivo expanded regulatory T cells in an autoimmune hepatitis murine model restores peripheral tolerance. Hepatology. 2013;57:217-27 pubmed publisher..Autologous infusion of ex vivo expanded CXCR3(+) Tregs in AIH patients could be an effective therapeutic approach to restore peripheral tolerance and induce remission of AIH. ..
- Williams D, Bonilla M, Gladyshev V, Salinas G. Thioredoxin glutathione reductase-dependent redox networks in platyhelminth parasites. Antioxid Redox Signal. 2013;19:735-45 pubmed publisher..Optimization of TGR inhibitors and identification of compounds targeting other parasite redox enzymes are good options to clinically develop relevant drugs for these neglected, but important diseases. ..