Gray J

References (7)

Title : Ascertaining the biochemical function of an essential pectin methylesterase in the gut microbe Bacteroides thetaiotaomicron - Duan_2020_J.Biol.Chem_295_18625
Author(s) : Duan CJ , Basl A , Liberato MV , Gray J , Nepogodiev SA , Field RA , Juge N , Ndeh D
Ref : Journal of Biological Chemistry , 295 :18625 , 2020
Abstract : Pectins are a major dietary nutrient source for the human gut microbiota (HGM). The prominent gut microbe Bacteroides thetaiotaomicron was recently shown to encode the founding member (BT1017) of a new family of pectin methylesterases (PMEs) essential for the metabolism of the complex pectin rhamnogalacturonan-II (RG-II). However, biochemical and structural knowledge of this family is lacking. Here, we showed that BT1017 is critical for the metabolism of an RG-II-derived oligosaccharide deltaBT1017oligoB generated by a BT1017 deletion mutant (deltaBT1017) during growth on carbohydrate extract from apple juice. Structural analyses of deltaBT1017oligoB using a combination of enzymatic, mass spectrometric and nuclear magnetic resonance approaches revealed that it is a bi-methylated nona-oligosaccharide GlcA-beta1,4-(2-O-Me-Xyl-alpha1,3)-Fuc-alpha1,4-(GalA-beta1,3)-Rha-alpha1,3-Api-beta1,2-(Araf-alpha1,3)-(GalA-alpha1,4)-GalA containing components of the RG-II backbone and its side chains. We showed that the catalytic module of BT1017 adopts an alpha/beta (alpha/beta) hydrolase fold, consisting of a central twisted 10-stranded beta-sheet sandwiched by several alpha-helices. This constitutes a new fold for PMEs, which are predominantly right-handed beta-helical proteins. Bioinformatics analyses revealed that the family is dominated by sequences from the prominent genera of the HGM, including Bacteroides and Prevotella Our results not only highlight the critical role played by this family of enzymes in pectin metabolism but provide new insights into the molecular basis of the adaptation of B. thetaiotaomicron to the human gut.
ESTHER : Duan_2020_J.Biol.Chem_295_18625
PubMedSearch : Duan_2020_J.Biol.Chem_295_18625
PubMedID: 33097594
Gene_locus related to this paper: bactn-q8a900

Title : Complex pectin metabolism by gut bacteria reveals novel catalytic functions - Ndeh_2017_Nature_544_65
Author(s) : Ndeh D , Rogowski A , Cartmell A , Luis AS , Basle A , Gray J , Venditto I , Briggs J , Zhang X , Labourel A , Terrapon N , Buffetto F , Nepogodiev S , Xiao Y , Field RA , Zhu Y , O'Neil MA , Urbanowicz BR , York WS , Davies GJ , Abbott DW , Ralet MC , Martens EC , Henrissat B , Gilbert HJ
Ref : Nature , 544 :65 , 2017
Abstract : The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron uses the most structurally complex glycan known: the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but 1 of its 21 distinct glycosidic linkages. The deconstruction of rhamnogalacturonan-II side chains and backbone are coordinated to overcome steric constraints, and the degradation involves previously undiscovered enzyme families and catalytic activities. The degradation system informs revision of the current structural model of rhamnogalacturonan-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycan in the human diet.
ESTHER : Ndeh_2017_Nature_544_65
PubMedSearch : Ndeh_2017_Nature_544_65
PubMedID: 28329766

Title : Donepezil in Parkinson's disease dementia: a randomized, double-blind efficacy and safety study - Dubois_2012_Mov.Disord_27_1230
Author(s) : Dubois B , Tolosa E , Katzenschlager R , Emre M , Lees AJ , Schumann G , Pourcher E , Gray J , Thomas G , Swartz J , Hsu T , Moline ML
Ref : Movement Disordersord , 27 :1230 , 2012
Abstract : Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+; global function). Secondary end points measured executive function, attention, activities of daily living (ADLs), and behavioral symptoms. Safety and tolerability were assessed. ADAS-cog mean changes from baseline to week 24 (end point) were not significant for donepezil in the intent-to-treat population by the predefined statistical model (difference from placebo: -1.45, P = .050, for 5 mg; -1.45, P = .076, for 10 mg). Alternative ADAS-cog analysis, removing the treatment-by-country interaction term from the model, revealed significant, dose-dependent benefit with donepezil (difference from placebo: -2.08, P = .002, for 5 mg; -3.31, P < .001, for 10 mg). The 10-mg group, but not the 5-mg group, had significantly better CIBIC+ scores compared with placebo (3.7 vs 3.9, P = .113, for 5 mg; 3.6 vs 3.9, P = .040, for 10 mg). Secondary end points-Mini-Mental State Exam; Delis-Kaplan Executive Function System; Brief Test of Attention, representing cognitive functions particularly relevant to PDD-showed significant benefit for both donepezil doses (P <= .007). There were no significant differences in ADLs or behavior. Adverse events were more common with donepezil but mostly mild/moderate in severity. Although the study did not achieve its predefined primary end points, it presents evidence suggesting that donepezil can improve cognition, executive function, and global status in PDD. Tolerability was consistent with the known safety profile of donepezil. (c) 2012 Movement Disorder Society.
ESTHER : Dubois_2012_Mov.Disord_27_1230
PubMedSearch : Dubois_2012_Mov.Disord_27_1230
PubMedID: 22915447

Title : Complete genome sequence of the oral pathogenic Bacterium porphyromonas gingivalis strain W83 - Nelson_2003_J.Bacteriol_185_5591
Author(s) : Nelson KE , Fleischmann RD , DeBoy RT , Paulsen IT , Fouts DE , Eisen JA , Daugherty SC , Dodson RJ , Durkin AS , Gwinn M , Haft DH , Kolonay JF , Nelson WC , Mason T , Tallon L , Gray J , Granger D , Tettelin H , Dong H , Galvin JL , Duncan MJ , Dewhirst FE , Fraser CM
Ref : Journal of Bacteriology , 185 :5591 , 2003
Abstract : The complete 2,343,479-bp genome sequence of the gram-negative, pathogenic oral bacterium Porphyromonas gingivalis strain W83, a major contributor to periodontal disease, was determined. Whole-genome comparative analysis with other available complete genome sequences confirms the close relationship between the Cytophaga-Flavobacteria-Bacteroides (CFB) phylum and the green-sulfur bacteria. Within the CFB phyla, the genomes most similar to that of P. gingivalis are those of Bacteroides thetaiotaomicron and B. fragilis. Outside of the CFB phyla the most similar genome to P. gingivalis is that of Chlorobium tepidum, supporting the previous phylogenetic studies that indicated that the Chlorobia and CFB phyla are related, albeit distantly. Genome analysis of strain W83 reveals a range of pathways and virulence determinants that relate to the novel biology of this oral pathogen. Among these determinants are at least six putative hemagglutinin-like genes and 36 previously unidentified peptidases. Genome analysis also reveals that P. gingivalis can metabolize a range of amino acids and generate a number of metabolic end products that are toxic to the human host or human gingival tissue and contribute to the development of periodontal disease.
ESTHER : Nelson_2003_J.Bacteriol_185_5591
PubMedSearch : Nelson_2003_J.Bacteriol_185_5591
PubMedID: 12949112
Gene_locus related to this paper: 9gamm-q4a538 , porgi-DPP , porgi-q7mtk3 , porgi-q7mu18 , porgi-q7mub3 , porgi-q7muw6 , porgi-q7mvp4 , porgi-q7mwa7 , porgi-q7mx03

Title : A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome - Mural_2002_Science_296_1661
Author(s) : Mural RJ , Adams MD , Myers EW , Smith HO , Miklos GL , Wides R , Halpern A , Li PW , Sutton GG , Nadeau J , Salzberg SL , Holt RA , Kodira CD , Lu F , Chen L , Deng Z , Evangelista CC , Gan W , Heiman TJ , Li J , Li Z , Merkulov GV , Milshina NV , Naik AK , Qi R , Shue BC , Wang A , Wang J , Wang X , Yan X , Ye J , Yooseph S , Zhao Q , Zheng L , Zhu SC , Biddick K , Bolanos R , Delcher AL , Dew IM , Fasulo D , Flanigan MJ , Huson DH , Kravitz SA , Miller JR , Mobarry CM , Reinert K , Remington KA , Zhang Q , Zheng XH , Nusskern DR , Lai Z , Lei Y , Zhong W , Yao A , Guan P , Ji RR , Gu Z , Wang ZY , Zhong F , Xiao C , Chiang CC , Yandell M , Wortman JR , Amanatides PG , Hladun SL , Pratts EC , Johnson JE , Dodson KL , Woodford KJ , Evans CA , Gropman B , Rusch DB , Venter E , Wang M , Smith TJ , Houck JT , Tompkins DE , Haynes C , Jacob D , Chin SH , Allen DR , Dahlke CE , Sanders R , Li K , Liu X , Levitsky AA , Majoros WH , Chen Q , Xia AC , Lopez JR , Donnelly MT , Newman MH , Glodek A , Kraft CL , Nodell M , Ali F , An HJ , Baldwin-Pitts D , Beeson KY , Cai S , Carnes M , Carver A , Caulk PM , Center A , Chen YH , Cheng ML , Coyne MD , Crowder M , Danaher S , Davenport LB , Desilets R , Dietz SM , Doup L , Dullaghan P , Ferriera S , Fosler CR , Gire HC , Gluecksmann A , Gocayne JD , Gray J , Hart B , Haynes J , Hoover J , Howland T , Ibegwam C , Jalali M , Johns D , Kline L , Ma DS , MacCawley S , Magoon A , Mann F , May D , McIntosh TC , Mehta S , Moy L , Moy MC , Murphy BJ , Murphy SD , Nelson KA , Nuri Z , Parker KA , Prudhomme AC , Puri VN , Qureshi H , Raley JC , Reardon MS , Regier MA , Rogers YH , Romblad DL , Schutz J , Scott JL , Scott R , Sitter CD , Smallwood M , Sprague AC , Stewart E , Strong RV , Suh E , Sylvester K , Thomas R , Tint NN , Tsonis C , Wang G , Williams MS , Williams SM , Windsor SM , Wolfe K , Wu MM , Zaveri J , Chaturvedi K , Gabrielian AE , Ke Z , Sun J , Subramanian G , Venter JC , Pfannkoch CM , Barnstead M , Stephenson LD
Ref : Science , 296 :1661 , 2002
Abstract : The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.
ESTHER : Mural_2002_Science_296_1661
PubMedSearch : Mural_2002_Science_296_1661
PubMedID: 12040188
Gene_locus related to this paper: mouse-ABH15 , mouse-Ces3b , mouse-Ces4a , mouse-dpp4 , mouse-FAP , mouse-Lipg , mouse-Q8C1A9 , mouse-rbbp9 , mouse-SERHL , mouse-SPG21 , mouse-w4vsp6

Title : Effects of the novel acetylcholinesterase inhibitor SDZ ENA 713 on sleep in man - Holsboer-Trachsler_1993_Neuropsychopharmacology_8_87
Author(s) : Holsboer-Trachsler E , Hatzinger M , Stohler R , Hemmeter U , Gray J , Muller J , Kocher R , Spiegel R
Ref : Neuropsychopharmacology , 8 :87 , 1993
Abstract : A novel brain-selective acetylcholinesterase inhibitor, SDZ ENA 713, is under development for the treatment of dementia of the Alzheimer type. To determine the threshold dose for central activity, single doses of the compound were administered to 20 young male volunteers in a double-blind cross-over design and the effects on the sleep electroencephalography studied. The first group of eight volunteers received in random order: placebo, 0.5 mg; and 1 mg SDZ ENA 713. The second group of 12 volunteers received: placebo, 1.3 mg; and 2 mg SDZ ENA 713. Sleep quality was not affected by the study medication, which was well tolerated by all subjects. A statistically significant increase in rapid-eye movement sleep density was observed after doses of 1 mg, 1.3 mg, and 2 mg. Rapid-eye movement latency and slow-wave sleep were not altered. The results demonstrate that SDZ ENA 713 is centrally active in man at well-tolerated doses.
ESTHER : Holsboer-Trachsler_1993_Neuropsychopharmacology_8_87
PubMedSearch : Holsboer-Trachsler_1993_Neuropsychopharmacology_8_87
PubMedID: 8424849

Title : Pharmacologic and clinicopharmacologic properties of SDZ ENA 713, a centrally selective acetylcholinesterase inhibitor -
Author(s) : Enz A , Boddeke H , Gray J , Spiegel R
Ref : Annals of the New York Academy of Sciences , 640 :272 , 1991
PubMedID: 1776750