Computational Exploration of the Medium-Chain Dehydrogenase / Reductase Superfamily
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Dehydrogenase Gene of Entamoeba Histolytica
Proc. Nad. Acad. Sci. USA Vol. 89, pp. 10188-10192, November 1992 Medical Sciences Cloning and expression of an NADP+-dependent alcohol dehydrogenase gene of Entamoeba histolytica (amebiasis/protozoan parasite/fermentation/inhibitors) AJIT KUMAR*, PEI-SHEN SHENtt, STEVEN DESCOTEAUX*, JAN POHL§, GORDON BAILEYt, AND JOHN SAMUELSON*1II *Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115; tDepartment of Biochemistry, Morehouse School of Medicine, Atlanta, GA 30310; §Microchemical Facility, Emory University, Atlanta, GA 30322; and 'Department of Pathology, New England Deaconess Hospital, Boston, MA 02215 Communicated by Elkan Blout, June 29, 1992 (receivedfor review May 1, 1992) ABSTRACT Ethanol is the major metabolic product of NAD(P)+ so that the reducing equivalents are regenerated glucose fermentation by the protozoan parasite Entmoeba (4-7). Both NADP+-dependent and NAD+-dependent alco- histolytica under the anaerobic conditions found in the lumen hol dehydrogenase (ADH) activities have been identified in of the colon. Here an internal peptide sequence determined E. histolytica trophozoites (4-7). The NADP+-dependent from a major 39-kDa amoeba protein isolated by isoeLtric ADH (EhADHi; EC 1.1.1.2) was found to be composed of focusing followed by SDS/PAGE was used to clone the gene for four -30-kDa subunits, prefer secondary alcohols to primary the E. histolytica NADP+-dependent alcohol dehydrogenase alcohols, and be inhibited by the substrate analogue pyrazole (EhADH1; EC 1.1.1.2). The EhADHi clone had an open (7). The amoeba NAD+-dependent ADH (EC 1.1.1.1) is not reading frame that was 360 amino acids long and encoded a well-characterized (4). -
Isyte: Integrated Systems Tool for Eye Gene Discovery
Lens iSyTE: Integrated Systems Tool for Eye Gene Discovery Salil A. Lachke,1,2,3,4 Joshua W. K. Ho,1,4,5 Gregory V. Kryukov,1,4,6 Daniel J. O’Connell,1 Anton Aboukhalil,1,7 Martha L. Bulyk,1,8,9 Peter J. Park,1,5,10 and Richard L. Maas1 PURPOSE. To facilitate the identification of genes associated ther investigation. Extension of this approach to other ocular with cataract and other ocular defects, the authors developed tissue components will facilitate eye disease gene discovery. and validated a computational tool termed iSyTE (integrated (Invest Ophthalmol Vis Sci. 2012;53:1617–1627) DOI: Systems Tool for Eye gene discovery; http://bioinformatics. 10.1167/iovs.11-8839 udel.edu/Research/iSyTE). iSyTE uses a mouse embryonic lens gene expression data set as a bioinformatics filter to select candidate genes from human or mouse genomic regions impli- ven with the advent of high-throughput sequencing, the cated in disease and to prioritize them for further mutational Ediscovery of genes associated with congenital birth defects and functional analyses. such as eye defects remains a challenge. We sought to develop METHODS. Microarray gene expression profiles were obtained a straightforward experimental approach that could facilitate for microdissected embryonic mouse lens at three key devel- the identification of candidate genes for developmental disor- opmental time points in the transition from the embryonic day ders, and, as proof-of-principle, we chose defects involving the (E)10.5 stage of lens placode invagination to E12.5 lens primary ocular lens. Opacification of the lens results in cataract, a leading cause of blindness that affects 77 million persons and fiber cell differentiation. -
The Failure of Two Major Formaldehyde Catabolism Enzymes (ADH5 and ALDH2) Leads to Partial Synthetic Lethality in C57BL/ 6 Mice Jun Nakamura1,2*, Darcy W
Nakamura et al. Genes and Environment (2020) 42:21 https://doi.org/10.1186/s41021-020-00160-4 SHORT REPORT Open Access The failure of two major formaldehyde catabolism enzymes (ADH5 and ALDH2) leads to partial synthetic lethality in C57BL/ 6 mice Jun Nakamura1,2*, Darcy W. Holley3, Toshihiro Kawamoto4 and Scott J. Bultman3 Abstract Background: Exogenous formaldehyde is classified by the IARC as a Category 1 known human carcinogen. Meanwhile, a significant amount of endogenous formaldehyde is produced in the human body; as such, formaldehyde-derived DNA and protein adducts have been detected in animals and humans in the absence of major exogenous formaldehyde exposure. However, the toxicological effects of endogenous formaldehyde on individuals with normal DNA damage repair functions are not well understood. In this study, we attempted to generate C57BL/6 mice deficient in both Adh5 and Aldh2, which encode two major enzymes that metabolize endogenous formaldehyde, in order to understand the effects of endogenous formaldehyde on mice with normal DNA repair function. Results: Due to deficiencies in both ADH5 and ALDH2, few mice survived past post-natal day 21. In fact, the survival of pups within the first few days after birth was significantly decreased. Remarkably, two Aldh2−/−/Adh5−/− mice survived for 25 days after birth, and we measured their total body weight and organ weights. The body weight of Aldh2−/−/Adh5−/− mice decreased significantly by almost 37% compared to the Aldh2−/−/Adh5+/− and Aldh2−/−/Adh5+/+ mice of the same litter. In addition, the absolute weight of each organ was also significantly reduced. Conclusion: Mice deficient in both formaldehyde-metabolizing enzymes ADH5 and ALDH2 were found to develop partial synthetic lethality and mortality shortly after birth. -
Age-Dependent Protein Abundance of Cytosolic Alcohol and Aldehyde Dehydrogenases in Human Liver S
Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2017/08/21/dmd.117.076463.DC2 http://dmd.aspetjournals.org/content/suppl/2017/06/12/dmd.117.076463.DC1 1521-009X/45/9/1044–1048$25.00 https://doi.org/10.1124/dmd.117.076463 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 45:1044–1048, September 2017 Copyright ª 2017 by The American Society for Pharmacology and Experimental Therapeutics Age-dependent Protein Abundance of Cytosolic Alcohol and Aldehyde Dehydrogenases in Human Liver s Deepak Kumar Bhatt, Andrea Gaedigk, Robin E. Pearce, J. Steven Leeder, and Bhagwat Prasad Department of Pharmaceutics, University of Washington, Seattle, Washington (D.K.B., B.P.); Department of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy-Kansas City, Missouri and School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri (A.G., R.E.P., J.S.L.) Received April 21, 2017; accepted June 5, 2017 ABSTRACT Hepatic cytosolic alcohol and aldehyde dehydrogenases (ADHs and the adult levels, respectively. For all proteins, the abundance steeply ALDHs) catalyze the biotransformation of xenobiotics (e.g., cyclo- increased during the first year of life, which mostly reached adult Downloaded from phosphamide and ethanol) and vitamin A. Because age-dependent levels during early childhood (age between 1 and 6 years). Only for hepatic abundance of these proteins is unknown, we quantified ADH1A protein abundance in adults (age > 18 year) was ∼40% lower protein expression of ADHs and ALDH1A1 in a large cohort of pediatric relative to the early childhood group. Abundances of ADHs and and adult human livers by liquid chromatography coupled with tandem ALDH1A1 were not associated with sex in samples with age > 1 year mass spectrometry proteomics. -
Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database. -
Transcriptomic and Genetic Associations Between Alzheimer's
cancers Article Transcriptomic and Genetic Associations between Alzheimer’s Disease, Parkinson’s Disease, and Cancer Jaume Forés-Martos 1,2,3, Cesar Boullosa 4,†, David Rodrigo-Domínguez 5,† , Jon Sánchez-Valle 6,† , Beatriz Suay-García 2,3 , Joan Climent 2,7 , Antonio Falcó 2,3 , Alfonso Valencia 6,8, Joan Anton Puig-Butillé 9,10, Susana Puig 10,11 and Rafael Tabarés-Seisdedos 1,12,13,* 1 Biomedical Research Networking Center of Mental Health (CIBERSAM), 28029 Madrid, Spain; [email protected] 2 ESI International Chair@CEU-UCH, Universidad Cardenal Herrera-CEU, CEU Universities, San Bartolomé 55, 46115 Alfara del Patriarca, Spain; [email protected] (B.S.-G.); [email protected] (J.C.); [email protected] (A.F.) 3 Departamento de Matemáticas, Física y Ciencias Tecnológicas, Universidad Cardenal Herrera-CEU, CEU Universities, San Bartolomé 55, 46115 Alfara del Patriarca, Spain 4 IES Miguel Catalán, 28823 Coslada, Spain; [email protected] 5 Consorcio Hospital General de Valencia, Servicio de Medicina Interna, 46014 Valencia, Spain; [email protected] 6 Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain; [email protected] (J.S.-V.); [email protected] (A.V.) 7 Departamento de Producción y Sanidad Animal, Salud Pública Veterinaria y Ciencia y Tecnología de los Citation: Forés-Martos, J.; Alimentos, Universidad Cardenal Herrera-CEU, CEU Universities, C/Tirant lo Blanc 7, Boullosa, C.; Rodrigo-Domínguez, D.; 46115 Alfara del Patriarca, Spain 8 Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain Sánchez-Valle, J.; Suay-García, B.; 9 Biochemical and Molecular Genetics Service, Hospital Clínic and August Pi i Sunyer Biomedical Research Climent, J.; Falcó, A.; Valencia, A.; Institute (IDIBAPS), 08036 Barcelona, Spain; [email protected] Puig-Butillé, J.A.; Puig, S.; et al. -
Alcohol-Responsive Genes Identified in Human Ipsc-Derived Neural Cultures
bioRxiv preprint doi: https://doi.org/10.1101/381673; this version posted July 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Alcohol-responsive genes identified in human iPSC-derived neural cultures Kevin P. Jensen1,2,#, Richard Lieberman3,#, Henry R. Kranzler4,5, Joel Gelernter1,2, and Jonathan Covault3,6* 1 Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511 2 VA Connecticut Healthcare System, West Haven, CT 06516 3 Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT 06030-1410 4 Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA 19104 5 VISN4 MIRECC, Crescenz VAMC, Philadelphia, PA 19104 6 Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269 # These authors contributed equally to this work *Correspondence: Department of Psychiatry UCONN Health 263 Farmington Avenue Farmington, CT 06030-1410 Telephone: 860-679-7560 Fax: 860-679-1296 Email: [email protected] Running title: Transcriptional effects of alcohol in human neural cultures 1 bioRxiv preprint doi: https://doi.org/10.1101/381673; this version posted July 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. -
The Genetics of Alcohol Dependence: Advancing Towards Systems-Based Approaches
Drug and Alcohol Dependence 125 (2012) 179–191 Contents lists available at SciVerse ScienceDirect Drug and Alcohol Dependence jo urnal homepage: www.elsevier.com/locate/drugalcdep Review The genetics of alcohol dependence: Advancing towards systems-based approaches a,b,c,∗ a,b,c a,d e f g a,b R.H.C. Palmer , J.E. McGeary , S. Francazio , B.J. Raphael , A.D. Lander , A.C. Heath , V.S. Knopik a Division of Behavioral Genetics, Department of Psychiatry at Rhode Island Hospital, United States b Department of Psychiatry and Human Behavior at the Warren Alpert Medical School of Brown University, United States c Department of Veterans Affairs, Providence, RI, United States d Providence College, Providence, United States e Department of Computer Science, and Center for Computational Molecular Biology, Brown University, United States f Department of Developmental and Cell Biology, University of California, Irvine, United States g Department of Psychiatry, Washington University School of Medicine, St. Louis, United States a r t i c l e i n f o a b s t r a c t Article history: Background: Personalized treatment for psychopathologies, in particular alcoholism, is highly dependent Received 7 February 2012 upon our ability to identify patterns of genetic and environmental effects that influence a person’s risk. Received in revised form 9 July 2012 Unfortunately, array-based whole genome investigations into heritable factors that explain why one Accepted 10 July 2012 person becomes dependent upon alcohol and another does not, have indicated that alcohol’s genetic Available online 31 July 2012 architecture is highly complex. -
Confirmation of Pathogenic Mechanisms by SARS-Cov-2–Host
Messina et al. Cell Death and Disease (2021) 12:788 https://doi.org/10.1038/s41419-021-03881-8 Cell Death & Disease ARTICLE Open Access Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2–host interactome Francesco Messina 1, Emanuela Giombini1, Chiara Montaldo1, Ashish Arunkumar Sharma2, Antonio Zoccoli3, Rafick-Pierre Sekaly2, Franco Locatelli4, Alimuddin Zumla5, Markus Maeurer6,7, Maria R. Capobianchi1, Francesco Nicola Lauria1 and Giuseppe Ippolito 1 Abstract In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level, but the mechanisms of interaction between host and SARS-CoV-2, determining the grade of COVID-19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred, applying an explorative algorithm (Random Walk with Restart, RWR) triggered by 28 proteins of SARS-CoV-2. The analysis of PPI allowed to estimate the distribution of SARS-CoV-2 proteins in the host cell. Interactome built around one single viral protein allowed to define a different response, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, the network-based approach highlighted a possible direct action of ORF3a and NS7b to enhancing Bradykinin Storm. This network-based representation of SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; clinical outcomes. -
How Is Alcohol Metabolized by the Body?
Overview: How Is Alcohol Metabolized by the Body? Samir Zakhari, Ph.D. Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase. Variations in the genes for these enzymes have been found to influence alcohol consumption, alcohol-related tissue damage, and alcohol dependence. The consequences of alcohol metabolism include oxygen deficits (i.e., hypoxia) in the liver; interaction between alcohol metabolism byproducts and other cell components, resulting in the formation of harmful compounds (i.e., adducts); formation of highly reactive oxygen-containing molecules (i.e., reactive oxygen species [ROS]) that can damage other cell components; changes in the ratio of NADH to NAD+ (i.e., the cell’s redox state); tissue damage; fetal damage; impairment of other metabolic processes; cancer; and medication interactions. Several issues related to alcohol metabolism require further research. KEY WORDS: Ethanol-to acetaldehyde metabolism; alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); acetaldehyde; acetate; cytochrome P450 2E1 (CYP2E1); catalase; reactive oxygen species (ROS); blood alcohol concentration (BAC); liver; stomach; brain; fetal alcohol effects; genetics and heredity; ethnic group; hypoxia The alcohol elimination rate varies state of liver cells. Chronic alcohol con- he effects of alcohol (i.e., ethanol) widely (i.e., three-fold) among individ- sumption and alcohol metabolism are on various tissues depend on its uals and is influenced by factors such as strongly linked to several pathological concentration in the blood T chronic alcohol consumption, diet, age, consequences and tissue damage. (blood alcohol concentration [BAC]) smoking, and time of day (Bennion and Understanding the balance of alcohol’s over time. -
Bioinformatic Protein Family Characterisation
Linköping studies in science and technology Dissertation No. 1343 Bioinformatic protein family characterisation Joel Hedlund Department of Physics, Chemistry and Biology Linköping, 2010 1 The front cover shows a tree diagram of the relations between proteins in the MDR superfamily (papers III–IV), excluding non-eukaryotic sequences as well as four fifths of the remainder for clarity. In total, 518 out of the 16667 known members are shown, and 1.5 cm in the dendrogram represents 10 % sequence differences. The bottom bar diagram shows conservation in these sequences using the CScore algorithm from the MSAView program (papers II and V), with infrequent insertions omitted for brevity. This example illustrates the size and complexity of the MDR superfamily, and it also serves as an illuminating example of the intricacies of the field of bioinformatics as a whole, where, after scaling down and removing layer after layer of complexity, there is still always ample size and complexity left to go around. The back cover shows a schematic view of the three-dimensional structure of human class III alcohol dehydrogenase, indicating the positions of the zinc ion and NAD cofactors, as well as the Rossmann fold cofactor binding domain (red) and the GroES-like folding core of the catalytic domain (green). This thesis was typeset using LYX. Inkscape was used for figure layout. During the course of research underlying this thesis, Joel Hedlund was enrolled in Forum Scientium, a multidisciplinary doctoral programme at Linköping University, Sweden. Copyright © 2010 Joel Hedlund, unless otherwise noted. All rights reserved. Joel Hedlund Bioinformatic protein family characterisation ISBN: 978-91-7393-297-4 ISSN: 0345-7524 Linköping studies in science and technology, dissertation No. -
A Detailed Genome-Wide Reconstruction of Mouse Metabolism Based on Human Recon 1
UC San Diego UC San Diego Previously Published Works Title A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1 Permalink https://escholarship.org/uc/item/0ck1p05f Journal BMC Systems Biology, 4(1) ISSN 1752-0509 Authors Sigurdsson, Martin I Jamshidi, Neema Steingrimsson, Eirikur et al. Publication Date 2010-10-19 DOI http://dx.doi.org/10.1186/1752-0509-4-140 Supplemental Material https://escholarship.org/uc/item/0ck1p05f#supplemental Peer reviewed eScholarship.org Powered by the California Digital Library University of California Sigurdsson et al. BMC Systems Biology 2010, 4:140 http://www.biomedcentral.com/1752-0509/4/140 RESEARCH ARTICLE Open Access A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1 Martin I Sigurdsson1,2,3, Neema Jamshidi4, Eirikur Steingrimsson1,3, Ines Thiele3,5*, Bernhard Ø Palsson3,4* Abstract Background: Well-curated and validated network reconstructions are extremely valuable tools in systems biology. Detailed metabolic reconstructions of mammals have recently emerged, including human reconstructions. They raise the question if the various successful applications of microbial reconstructions can be replicated in complex organisms. Results: We mapped the published, detailed reconstruction of human metabolism (Recon 1) to other mammals. By searching for genes homologous to Recon 1 genes within mammalian genomes, we were able to create draft metabolic reconstructions of five mammals, including the mouse. Each draft reconstruction was created in compartmentalized and non-compartmentalized version via two different approaches. Using gap-filling algorithms, we were able to produce all cellular components with three out of four versions of the mouse metabolic reconstruction.