6d6w › Citations

Three structurally and functionally distinct β-glucuronidases from the human gut microbe Bacteroides uniformis.

Pellock SJ, Walton WG, Biernat KA, Torres-Rivera D, Creekmore BC, Xu Y, Liu J, Tripathy A, Stewart LJ, Redinbo MR
J Biol Chem 293 18559-18573 (2018)
Related entries: 6d1n, 6d1p, 6d41, 6d50, 6d7f, 6d89, 6d8g, 6d8k

Cited: 31 times
EuropePMC logo PMID: 30301767

Abstract

The glycoside hydrolases encoded by the human gut microbiome play an integral role in processing a variety of exogenous and endogenous glycoconjugates. Here we present three structurally and functionally distinct β-glucuronidase (GUS) glycoside hydrolases from a single human gut commensal microbe, Bacteroides uniformis We show using nine crystal structures, biochemical, and biophysical data that whereas these three proteins share similar overall folds, they exhibit different structural features that create three structurally and functionally unique enzyme active sites. Notably, quaternary structure plays an important role in creating distinct active site features that are hard to predict via structural modeling methods. The enzymes display differential processing capabilities toward glucuronic acid-containing polysaccharides and SN-38-glucuronide, a metabolite of the cancer drug irinotecan. We also demonstrate that GUS-specific and nonselective inhibitors exhibit varying potencies toward each enzyme. Together, these data highlight the diversity of GUS enzymes within a single Bacteroides gut commensal and advance our understanding of how structural details impact the specific roles microbial enzymes play in processing drug-glucuronide and glycan substrates.

Reviews - 6d6w mentioned but not cited (1)

  1. A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target. Fernández-Murga ML, Gil-Ortiz F, Serrano-García L, Llombart-Cussac A. Pathogens 12 1086 (2023)

Articles - 6d6w mentioned but not cited (1)

  1. Three structurally and functionally distinct β-glucuronidases from the human gut microbe Bacteroides uniformis. Pellock SJ, Walton WG, Biernat KA, Torres-Rivera D, Creekmore BC, Xu Y, Liu J, Tripathy A, Stewart LJ, Redinbo MR. J Biol Chem 293 18559-18573 (2018)


Reviews citing this publication (4)

  1. The Role of Gut Microbial β-Glucuronidase in Estrogen Reactivation and Breast Cancer. Sui Y, Wu J, Chen J. Front Cell Dev Biol 9 631552 (2021)
  2. A structural metagenomics pipeline for examining the gut microbiome. Walker ME, Simpson JB, Redinbo MR. Curr Opin Struct Biol 75 102416 (2022)
  3. Role of the microbiome in systemic therapy for pancreatic ductal adenocarcinoma (Review). Huang X, Li M, Hou S, Tian B. Int J Oncol 59 101 (2021)
  4. The role of gut microbial β-glucuronidase in drug disposition and development. Gao S, Sun R, Singh R, Yu So S, Chan CTY, Savidge T, Hu M. Drug Discov Today 27 103316 (2022)

Articles citing this publication (25)

  1. Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. Ervin SM, Li H, Lim L, Roberts LR, Liang X, Mani S, Redinbo MR. J Biol Chem 294 18586-18599 (2019)
  2. Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy. Bhatt AP, Pellock SJ, Biernat KA, Walton WG, Wallace BD, Creekmore BC, Letertre MM, Swann JR, Wilson ID, Roques JR, Darr DB, Bailey ST, Montgomery SA, Roach JM, Azcarate-Peril MA, Sartor RB, Gharaibeh RZ, Bultman SJ, Redinbo MR. Proc Natl Acad Sci U S A 117 7374-7381 (2020)
  3. Vancomycin relieves mycophenolate mofetil-induced gastrointestinal toxicity by eliminating gut bacterial β-glucuronidase activity. Taylor MR, Flannigan KL, Rahim H, Mohamud A, Lewis IA, Hirota SA, Greenway SC. Sci Adv 5 eaax2358 (2019)
  4. Discovering the Microbial Enzymes Driving Drug Toxicity with Activity-Based Protein Profiling. Jariwala PB, Pellock SJ, Goldfarb D, Cloer EW, Artola M, Simpson JB, Bhatt AP, Walton WG, Roberts LR, Major MB, Davies GJ, Overkleeft HS, Redinbo MR. ACS Chem Biol 15 217-225 (2020)
  5. Comparative Analysis of Microbial Community Structure and Function in the Gut of Wild and Captive Amur Tiger. Ning Y, Qi J, Dobbins MT, Liang X, Wang J, Chen S, Ma J, Jiang G. Front Microbiol 11 1665 (2020)
  6. Targeting Regorafenib-Induced Toxicity through Inhibition of Gut Microbial β-Glucuronidases. Ervin SM, Hanley RP, Lim L, Walton WG, Pearce KH, Bhatt AP, James LI, Redinbo MR. ACS Chem Biol 14 2737-2744 (2019)
  7. Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract. Zhang J, Walker ME, Sanidad KZ, Zhang H, Liang Y, Zhao E, Chacon-Vargas K, Yeliseyev V, Parsonnet J, Haggerty TD, Wang G, Simpson JB, Jariwala PB, Beaty VV, Yang J, Yang H, Panigrahy A, Minter LM, Kim D, Gibbons JG, Liu L, Li Z, Xiao H, Borlandelli V, Overkleeft HS, Cloer EW, Major MB, Goldfarb D, Cai Z, Redinbo MR, Zhang G. Nat Commun 13 136 (2022)
  8. Discovery and Characterization of FMN-Binding β-Glucuronidases in the Human Gut Microbiome. Pellock SJ, Walton WG, Ervin SM, Torres-Rivera D, Creekmore BC, Bergan G, Dunn ZD, Li B, Tripathy A, Redinbo MR. J Mol Biol 431 970-980 (2019)
  9. β-Glucuronidase Pattern Predicted From Gut Metagenomes Indicates Potentially Diversified Pharmacomicrobiomics. Candeliere F, Raimondi S, Ranieri R, Musmeci E, Zambon A, Amaretti A, Rossi M. Front Microbiol 13 826994 (2022)
  10. Predicting drug-metagenome interactions: Variation in the microbial β-glucuronidase level in the human gut metagenomes. Elmassry MM, Kim S, Busby B. PLoS One 16 e0244876 (2021)
  11. Coadministration of metformin prevents olanzapine-induced metabolic dysfunction and regulates the gut-liver axis in rats. Luo C, Wang X, Huang HX, Mao XY, Zhou HH, Liu ZQ. Psychopharmacology (Berl) 238 239-248 (2021)
  12. Differences in Fecal Microbiome and Antimicrobial Resistance between Captive and Free-Range Sika Deer under the Same Exposure of Antibiotic Anthelmintics. Wu K, Xu Y, Zhang W, Mao H, Chen B, Zheng Y, Hu X. Microbiol Spectr 9 e0191821 (2021)
  13. Selecting a Single Stereocenter: The Molecular Nuances That Differentiate β-Hexuronidases in the Human Gut Microbiome. Pellock SJ, Walton WG, Redinbo MR. Biochemistry 58 1311-1317 (2019)
  14. Functional metagenomic screening identifies an unexpected β-glucuronidase. Neun S, Brear P, Campbell E, Tryfona T, El Omari K, Wagner A, Dupree P, Hyvönen M, Hollfelder F. Nat Chem Biol 18 1096-1103 (2022)
  15. In-Silico Characterization of Estrogen Reactivating β-Glucuronidase Enzyme in GIT Associated Microbiota of Normal Human and Breast Cancer Patients. Muccee F, Ghazanfar S, Ajmal W, Al-Zahrani M. Genes (Basel) 13 1545 (2022)
  16. Metagenomics combined with activity-based proteomics point to gut bacterial enzymes that reactivate mycophenolate. Simpson JB, Sekela JJ, Graboski AL, Borlandelli VB, Bivins MM, Barker NK, Sorgen AA, Mordant AL, Johnson RL, Bhatt AP, Fodor AA, Herring LE, Overkleeft H, Lee JR, Redinbo MR. Gut Microbes 14 2107289 (2022)
  17. Modulation of Gut Microbiota Composition and Short-Chain Fatty Acid Synthesis by Mogroside V in an In Vitro Incubation System. Xiao R, Liao W, Luo G, Qin Z, Han S, Lin Y. ACS Omega 6 25486-25496 (2021)
  18. Correlation analysis between gut microbiota characteristics and melasma. Liu C, He D, Yu A, Deng Y, Wang L, Song Z. Front Microbiol 13 1051653 (2022)
  19. Synthesis, Biological Evaluation and Low-Toxic Formulation Development of Glycosylated Paclitaxel Prodrugs. Mao Y, Zhang Y, Luo Z, Zhan R, Xu H, Chen W, Huang H. Molecules 23 E3211 (2018)
  20. Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice. Letertre MPM, Bhatt AP, Harvey M, Nicholson JK, Wilson ID, Redinbo MR, Swann JR. Sci Rep 12 17435 (2022)
  21. Environmental Factors Influencing Phyllosphere Bacterial Communities in Giant Pandas' Staple Food Bamboos. Long J, Luo W, Xie J, Yuan Y, Wang J, Kang L, Li Y, Zhang Z, Hong M. Front Microbiol 12 748141 (2021)
  22. Virtual Screening for the Discovery of Microbiome β-Glucuronidase Inhibitors to Alleviate Cancer Drug Toxicity. Challa AP, Hu X, Zhang YQ, Hymes J, Wallace BD, Karavadhi S, Sun H, Patnaik S, Hall MD, Shen M. J Chem Inf Model 62 1783-1793 (2022)
  23. Editorial Analyzing the intestinal microbiome in inflammatory bowel disease: From RNA to multiomics. Lett B, Costello S, Roberts-Thomson I. JGH Open 4 779-781 (2020)
  24. Microbial β-glucuronidases drive human periodontal disease etiology. Lietzan AD, Simpson JB, Walton WG, Jariwala PB, Xu Y, Boynton MH, Liu J, Redinbo MR. Sci Adv 9 eadg3390 (2023)
  25. Structural and Biochemical Basis of a Marine Bacterial Glycoside Hydrolase Family 2 β-Glycosidase with Broad Substrate Specificity. Yang J, Li S, Liu Y, Li R, Long L. Appl Environ Microbiol 88 e0222621 (2022)


Quick links