1dpg › Citations

The three-dimensional structure of glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides refined at 2.0 A resolution.

Rowland P, Basak AK, Gover S, Levy HR, Adams MJ
Structure 2 1073-87 (1994)
Cited: 78 times
EuropePMC logo PMID: 7881907

Abstract

Background

Glucose 6-phosphate dehydrogenase (G6PD) is the first enzyme of the pentose phosphate pathway. Normally the pathway is synthetic and NADP-dependent, but the Gram-positive bacterium Leuconostoc mesenteroides, which does not have a complete glycolytic pathway, also uses the oxidative enzymes of the pentose phosphate pathway for catabolic reactions, and selects either NAD or NADP depending on the demands for catabolic or anabolic metabolism.

Results

The structure of G6PD has been determined and refined to 2.0 A resolution. The enzyme is a dimer, each subunit consisting of two domains. The smaller domain is a classic dinucleotide-binding fold, while the larger one is a new beta+ alpha fold, not previously seen, with a predominantly antiparallel nine-stranded beta-sheet. There are significant structural differences in the coenzyme-binding domains of the two subunits, caused by Pro 149 which is cis in one subunit and trans in the other.

Conclusion

The structure has allowed us to propose the location of the active site and the coenzyme-binding site, and suggests the role of many of the residues conserved between species. We propose that the conserved Arg46 would interact with both the adenine ring and the 2'-phosphate of NADP. Gln47, which is not conserved, may contribute to the change from NADP to dual coenzyme specificity. His178, in a nine-residue peptide conserved for all known sequences, binds a phosphate in the active site pocket. His240 is the most likely candidate for the base to oxidize the 1-hydroxyl group of the glucose 6-phosphate substrate.

Reviews - 1dpg mentioned but not cited (2)

  1. The Blueprint of a Minimal Cell: MiniBacillus. Reuß DR, Commichau FM, Gundlach J, Zhu B, Stülke J. Microbiol Mol Biol Rev 80 955-987 (2016)
  2. Structural and functional features of the NAD(P) dependent Gfo/Idh/MocA protein family oxidoreductases. Taberman H, Parkkinen T, Rouvinen J. Protein Sci 25 778-786 (2016)

Articles - 1dpg mentioned but not cited (11)

  1. Toward a resolution of the introns early/late debate: only phase zero introns are correlated with the structure of ancient proteins. de Souza SJ, Long M, Klein RJ, Roy S, Lin S, Gilbert W. Proc Natl Acad Sci U S A 95 5094-5099 (1998)
  2. Intron positions correlate with module boundaries in ancient proteins. de Souza SJ, Long M, Schoenbach L, Roy SW, Gilbert W. Proc Natl Acad Sci U S A 93 14632-14636 (1996)
  3. What role do surfaces play in GB models? A new-generation of surface-generalized born model based on a novel gaussian surface for biomolecules. Yu Z, Jacobson MP, Friesner RA. J Comput Chem 27 72-89 (2006)
  4. Prediction of Protein Loop Conformations using the AGBNP Implicit Solvent Model and Torsion Angle Sampling. Felts AK, Gallicchio E, Chekmarev D, Paris KA, Friesner RA, Levy RM. J Chem Theory Comput 4 855-868 (2008)
  5. Protein subunit interfaces: heterodimers versus homodimers. Zhanhua C, Gan JG, Lei L, Sakharkar MK, Kangueane P. Bioinformation 1 28-39 (2005)
  6. A bacterial checkpoint protein for ribosome assembly moonlights as an essential metabolite-proofreading enzyme. Sachla AJ, Helmann JD. Nat Commun 10 1526 (2019)
  7. Identification of essential amino acids in the Azorhizobium caulinodans fucosyltransferase NodZ. Chazalet V, Uehara K, Geremia RA, Breton C. J Bacteriol 183 7067-7075 (2001)
  8. Finding evolutionary relations beyond superfamilies: fold-based superfamilies. Matsuda K, Nishioka T, Kinoshita K, Kawabata T, Go N. Protein Sci 12 2239-2251 (2003)
  9. Identification and In Silico Characterization of Novel Helicobacter pylori Glucose-6-Phosphate Dehydrogenase Inhibitors. Hernández-Ochoa B, Navarrete-Vázquez G, Aguayo-Ortiz R, Ortiz-Ramírez P, Morales-Luna L, Martínez-Rosas V, González-Valdez A, Gómez-Chávez F, Enríquez-Flores S, Wong-Baeza C, Baeza-Ramírez I, Pérez de la Cruz V, Gómez-Manzo S. Molecules 26 4955 (2021)
  10. Implications of differential peroxyl radical-induced inactivation of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase for the pentose phosphate pathway. Reyes JS, Fuentes-Lemus E, Figueroa JD, Rojas J, Fierro A, Arenas F, Hägglund PM, Davies MJ, López-Alarcón C. Sci Rep 12 21191 (2022)
  11. Characterization of morphine-glucose-6-phosphate dehydrogenase conjugates by mass spectrometry. Chiu ML, Ytterberg AJ, Ogorzalek Loo RR, Loo JA, Monbouquette HG. Bioconjug Chem 22 1595-1604 (2011)


Reviews citing this publication (11)

  1. G6PD deficiency: the genotype-phenotype association. Mason PJ, Bautista JM, Gilsanz F. Blood Rev 21 267-283 (2007)
  2. Glucose-6-phosphate dehydrogenase deficiency. Mehta A, Mason PJ, Vulliamy TJ. Baillieres Best Pract Res Clin Haematol 13 21-38 (2000)
  3. A new lease of life for an old enzyme. Martini G, Ursini MV. Bioessays 18 631-637 (1996)
  4. Glucose-6-phosphate dehydrogenase--beyond the realm of red cell biology. Ho HY, Cheng ML, Chiu DT. Free Radic Res 48 1028-1048 (2014)
  5. The Multiple Roles of Glucose-6-Phosphate Dehydrogenase in Tumorigenesis and Cancer Chemoresistance. Song J, Sun H, Zhang S, Shan C. Life (Basel) 12 271 (2022)
  6. Chronic non-spherocytic haemolytic disorders associated with glucose-6-phosphate dehydrogenase variants. Fiorelli G, Martinez di Montemuros F, Cappellini MD. Baillieres Best Pract Res Clin Haematol 13 39-55 (2000)
  7. [Glucose 6-phosphate dehydrogenase deficiency: a protection against malaria and a risk for hemolytic accidents]. Wajcman H, Galactéros F. C R Biol 327 711-720 (2004)
  8. About hemoglobins, G6PD and parasites in red cells. Luzzatto L. Experientia 51 206-208 (1995)
  9. Boosting the Discovery of Small Molecule Inhibitors of Glucose-6-Phosphate Dehydrogenase for the Treatment of Cancer, Infectious Diseases, and Inflammation. Koperniku A, Garcia AA, Mochly-Rosen D. J Med Chem 65 4403-4423 (2022)
  10. Human genetics: past, present, and future, with special reference to major trends in Japan. Yanase T. Jpn J Hum Genet 42 265-316 (1997)
  11. Structure and function of aldopentose catabolism enzymes involved in oxidative non-phosphorylative pathways. Ren Y, Eronen V, Blomster Andberg M, Koivula A, Hakulinen N. Biotechnol Biofuels Bioprod 15 147 (2022)

Articles citing this publication (54)

  1. Molecular basis of sulfite oxidase deficiency from the structure of sulfite oxidase. Kisker C, Schindelin H, Pacheco A, Wehbi WA, Garrett RM, Rajagopalan KV, Enemark JH, Rees DC. Cell 91 973-983 (1997)
  2. Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an artificial swinging arm. Fu J, Yang YR, Johnson-Buck A, Liu M, Liu Y, Walter NG, Woodbury NW, Yan H. Nat Nanotechnol 9 531-536 (2014)
  3. Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP(+) molecule and provides insights into enzyme deficiency. Au SW, Gover S, Lam VM, Adams MJ. Structure 8 293-303 (2000)
  4. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion. Zhao Z, Fu J, Dhakal S, Johnson-Buck A, Liu M, Zhang T, Woodbury NW, Liu Y, Walter NG, Yan H. Nat Commun 7 10619 (2016)
  5. A DNA tweezer-actuated enzyme nanoreactor. Liu M, Fu J, Hejesen C, Yang Y, Woodbury NW, Gothelf K, Liu Y, Yan H. Nat Commun 4 2127 (2013)
  6. The geometry of domain combination in proteins. Bashton M, Chothia C. J Mol Biol 315 927-939 (2002)
  7. Structural diversity of domain superfamilies in the CATH database. Reeves GA, Dallman TJ, Redfern OC, Akpor A, Orengo CA. J Mol Biol 360 725-741 (2006)
  8. The structure of glucose-fructose oxidoreductase from Zymomonas mobilis: an osmoprotective periplasmic enzyme containing non-dissociable NADP. Kingston RL, Scopes RK, Baker EN. Structure 4 1413-1428 (1996)
  9. What is the role of the second "structural" NADP+-binding site in human glucose 6-phosphate dehydrogenase? Wang XT, Chan TF, Lam VM, Engel PC. Protein Sci 17 1403-1411 (2008)
  10. A new glucose-6-phosphate dehydrogenase variant, G6PD Orissa (44 Ala-->Gly), is the major polymorphic variant in tribal populations in India. Kaeda JS, Chhotray GP, Ranjit MR, Bautista JM, Reddy PH, Stevens D, Naidu JM, Britt RP, Vulliamy TJ, Luzzatto L. Am J Hum Genet 57 1335-1341 (1995)
  11. Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase. A novel bifunctional enzyme in malaria parasites. Clarke JL, Scopes DA, Sodeinde O, Mason PJ. Eur J Biochem 268 2013-2019 (2001)
  12. Human mutations in glucose 6-phosphate dehydrogenase reflect evolutionary history. Notaro R, Afolayan A, Luzzatto L. FASEB J 14 485-494 (2000)
  13. Molecular analysis of the gene encoding F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis. Purwantini E, Daniels L. J Bacteriol 180 2212-2219 (1998)
  14. The inter-ligand Overhauser effect: a powerful new NMR approach for mapping structural relationships of macromolecular ligands. Li D, DeRose EF, London RE. J Biomol NMR 15 71-76 (1999)
  15. Glucose-6-phosphate dehydrogenase from the hyperthermophilic bacterium Thermotoga maritima: expression of the g6pd gene and characterization of an extremely thermophilic enzyme. Hansen T, Schlichting B, Schönheit P. FEMS Microbiol Lett 216 249-253 (2002)
  16. G6PDdb, an integrated database of glucose-6-phosphate dehydrogenase (G6PD) mutations. Kwok CJ, Martin AC, Au SW, Lam VM. Hum Mutat 19 217-224 (2002)
  17. Inhibition of Trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites. Cordeiro AT, Thiemann OH, Michels PA. Bioorg Med Chem 17 2483-2489 (2009)
  18. Assembly of multienzyme complexes on DNA nanostructures. Fu J, Yang YR, Dhakal S, Zhao Z, Liu M, Zhang T, Walter NG, Yan H. Nat Protoc 11 2243-2273 (2016)
  19. Glucose-6-phosphate dehydrogenase partitioning in two-phase aqueous mixed (nonionic/cationic) micellar systems. Rangel-Yagui CO, Lam H, Kamei DT, Wang DI, Pessoa A, Blankschtein D. Biotechnol Bioeng 82 445-456 (2003)
  20. Recombinant human glucose-6-phosphate dehydrogenase. Evidence for a rapid-equilibrium random-order mechanism. Wang XT, Au SW, Lam VM, Engel PC. Eur J Biochem 269 3417-3424 (2002)
  21. Clinical and haematological consequences of recurrent G6PD mutations and a single new mutation causing chronic nonspherocytic haemolytic anaemia. Vulliamy TJ, Kaeda JS, Ait-Chafa D, Mangerini R, Roper D, Barbot J, Mehta AB, Athanassiou-Metaxa M, Luzzatto L, Mason PJ. Br J Haematol 101 670-675 (1998)
  22. Human glucose-6-phosphate dehydrogenase. Lysine 205 is dispensable for substrate binding but essential for catalysis. Bautista JM, Mason PJ, Luzzatto L. FEBS Lett 366 61-64 (1995)
  23. Irreversible inhibition of glucose-6-phosphate dehydrogenase by the coenzyme A conjugate of ketoprofen: a key to oxidative stress induced by non-steroidal anti-inflammatory drugs? Asensio C, Levoin N, Guillaume C, Guerquin MJ, Rouguieg K, Chrétien F, Chapleur Y, Netter P, Minn A, Lapicque F. Biochem Pharmacol 73 405-416 (2007)
  24. Probing the affinity and specificity of yeast alcohol dehydrogenase I for coenzymes. Fan F, Plapp BV. Arch Biochem Biophys 367 240-249 (1999)
  25. Redox regulation of chloroplastic G6PDH activity by thioredoxin occurs through structural changes modifying substrate accessibility and cofactor binding. Née G, Aumont-Nicaise M, Zaffagnini M, Nessler S, Valerio-Lepiniec M, Issakidis-Bourguet E. Biochem J 457 117-125 (2014)
  26. Pseudomonas fluorescens mannitol 2-dehydrogenase and the family of polyol-specific long-chain dehydrogenases/reductases: sequence-based classification and analysis of structure-function relationships. Klimacek M, Kavanagh KL, Wilson DK, Nidetzky B. Chem Biol Interact 143-144 559-582 (2003)
  27. The stereospecificity of hydrogen transfer to NAD(P)+ catalyzed by lactol dehydrogenases. Mostad SB, Helming HL, Groom C, Glasfeld A. Biochem Biophys Res Commun 233 681-686 (1997)
  28. Deletion of the glucose-6-phosphate dehydrogenase gene KlZWF1 affects both fermentative and respiratory metabolism in Kluyveromyces lactis. Saliola M, Scappucci G, De Maria I, Lodi T, Mancini P, Falcone C. Eukaryot Cell 6 19-27 (2007)
  29. Independent origin of single and double mutations in the human glucose 6-phosphate dehydrogenase gene. Vulliamy T, Rovira A, Yusoff N, Colomer D, Luzzatto L, Vives-Corrons JL. Hum Mutat 8 311-318 (1996)
  30. Protein partitioning in poly(ethylene glycol)/sodium polyacrylate aqueous two-phase systems. Johansson HO, Magaldi FM, Feitosa E, Pessoa A. J Chromatogr A 1178 145-153 (2008)
  31. Binding Mode and Selectivity of Steroids towards Glucose-6-phosphate Dehydrogenase from the Pathogen Trypanosoma cruzi. Ortiz C, Moraca F, Medeiros A, Botta M, Hamilton N, Comini MA. Molecules 21 368 (2016)
  32. Two new class III G6PD variants [G6PD Tunis (c.920A>C: p.307Gln>Pro) and G6PD Nefza (c.968T>C: p.323 Leu>Pro)] and overview of the spectrum of mutations in Tunisia. Benmansour I, Moradkhani K, Moumni I, Wajcman H, Hafsia R, Ghanem A, Abbès S, Préhu C. Blood Cells Mol Dis 50 110-114 (2013)
  33. Intersubunit disulfide interactions play a critical role in maintaining the thermostability of glucose-6-phosphate dehydrogenase from the hyperthermophilic bacterium Aquifex aeolicus. Nakka M, Iyer RB, Bachas LG. Protein J 25 17-21 (2006)
  34. Letter The structure of a Trypanosoma cruzi glucose-6-phosphate dehydrogenase reveals differences from the mammalian enzyme. Mercaldi GF, Dawson A, Hunter WN, Cordeiro AT. FEBS Lett 590 2776-2786 (2016)
  35. Amino acid conservation and clinical severity of human glucose-6-phosphate dehydrogenase mutations. Cheng YS, Tang TK, Hwang M. J Biomed Sci 6 106-114 (1999)
  36. Biochemical Characterization and Structural Modeling of Fused Glucose-6-Phosphate Dehydrogenase-Phosphogluconolactonase from Giardia lamblia. Morales-Luna L, Serrano-Posada H, González-Valdez A, Ortega-Cuellar D, Vanoye-Carlo A, Hernández-Ochoa B, Sierra-Palacios E, Rufino-González Y, Castillo-Rodríguez RA, Pérez de la Cruz V, Moreno-Vargas L, Prada-Gracia D, Marcial-Quino J, Gómez-Manzo S. Int J Mol Sci 19 E2518 (2018)
  37. Galactosyl-mimodye ligands for Pseudomonas fluorescens beta-galactose dehydrogenase. Mazitsos CF, Rigden DJ, Tsoungas PG, Clonis YD. Eur J Biochem 269 5391-5405 (2002)
  38. Several mutations including two novel mutations of the glucose-6-phosphate dehydrogenase gene in Polish G6PD deficient subjects with chronic nonspherocytic hemolytic anemia, acute hemolytic anemia, and favism. Jablonska-Skwiecinska E, Lewandowska I, Plochocka D, Topczewski J, Zimowski JG, Klopocka J, Burzynska B. Hum Mutat 14 477-484 (1999)
  39. Site directed immobilization of glucose-6-phosphate dehydrogenase via thiol-disulfide interchange: influence on catalytic activity of cysteines introduced at different positions. Simons JR, Mosisch M, Torda AE, Hilterhaus L. J Biotechnol 167 1-7 (2013)
  40. Crystal structure of a truncated mutant of glucose-fructose oxidoreductase shows that an N-terminal arm controls tetramer formation. Lott JS, Halbig D, Baker HM, Hardman MJ, Sprenger GA, Baker EN. J Mol Biol 304 575-584 (2000)
  41. Autodisplay of glucose-6-phosphate dehydrogenase for redox cofactor regeneration at the cell surface. Schüürmann J, Quehl P, Lindhorst F, Lang K, Jose J. Biotechnol Bioeng 114 1658-1669 (2017)
  42. Characterizing the Fused TvG6PD::6PGL Protein from the Protozoan Trichomonas vaginalis, and Effects of the NADP+ Molecule on Enzyme Stability. Morales-Luna L, Hernández-Ochoa B, Ramírez-Nava EJ, Martínez-Rosas V, Ortiz-Ramírez P, Fernández-Rosario F, González-Valdez A, Cárdenas-Rodríguez N, Serrano-Posada H, Centeno-Leija S, Arreguin-Espinosa R, Cuevas-Cruz M, Ortega-Cuellar D, Pérez de la Cruz V, Rocha-Ramírez LM, Sierra-Palacios E, Castillo-Rodríguez RA, Vega-García V, Rufino-González Y, Marcial-Quino J, Gómez-Manzo S. Int J Mol Sci 21 E4831 (2020)
  43. Cofactor Specificity of Glucose-6-Phosphate Dehydrogenase Isozymes in Pseudomonas putida Reveals a General Principle Underlying Glycolytic Strategies in Bacteria. Volke DC, Olavarría K, Nikel PI. mSystems 6 e00014-21 (2021)
  44. Genome sequences of Arthrobacter spp. that use a modified sulfoglycolytic Embden-Meyerhof-Parnas pathway. Kaur A, van der Peet PL, Mui JW, Herisse M, Pidot S, Williams SJ. Arch Microbiol 204 193 (2022)
  45. Molecular Cloning and Exploration of the Biochemical and Functional Analysis of Recombinant Glucose-6-Phosphate Dehydrogenase from Gluconoacetobacter diazotrophicus PAL5. Ramírez-Nava EJ, Ortega-Cuellar D, González-Valdez A, Castillo-Rodríguez RA, Ponce-Soto GY, Hernández-Ochoa B, Cárdenas-Rodríguez N, Martínez-Rosas V, Morales-Luna L, Serrano-Posada H, Sierra-Palacios E, Arreguin-Espinosa R, Cuevas-Cruz M, Rocha-Ramírez LM, Pérez de la Cruz V, Marcial-Quino J, Gómez-Manzo S. Int J Mol Sci 20 E5279 (2019)
  46. Use of two transcription starts in the G6PD gene of the bark beetle Ips typographus. Dolezelová E, Zurovec M, Böhmová M, Sehnal F. Insect Mol Biol 15 25-32 (2006)
  47. Cloning, expression, and characterization of a thermostable glucose-6-phosphate dehydrogenase from Thermoanaerobacter tengcongensis. Li Z, Jiang N, Yang K, Zheng J. Extremophiles 20 149-156 (2016)
  48. Biochemical and Kinetic Characterization of the Glucose-6-Phosphate Dehydrogenase from Helicobacter pylori Strain 29CaP. Ortiz-Ramírez P, Hernández-Ochoa B, Ortega-Cuellar D, González-Valdez A, Martínez-Rosas V, Morales-Luna L, Arreguin-Espinosa R, Castillo-Rodríguez RA, Canseco-Ávila LM, Cárdenas-Rodríguez N, Pérez de la Cruz V, Montiel-González AM, Gómez-Chávez F, Gómez-Manzo S. Microorganisms 10 1359 (2022)
  49. Kinetic and thermodynamic properties of two electrophoretically similar genetic variants of human erythrocyte glucose-6-phosphate dehydrogenase. Adediran SA. Biochimie 78 165-170 (1996)
  50. Anti-Heliobacter pylori and Anti-Inflammatory Potential of Salvia officinalis Metabolites: In Vitro and In Silico Studies. Alomar HA, Elkady WM, Abdel-Aziz MM, Ibrahim TA, Fathallah N. Metabolites 13 136 (2023)
  51. Cloning, Expression, and Characterization of a Psychrophilic Glucose 6-Phosphate Dehydrogenase from Sphingomonas sp. PAMC 26621. TranNgoc K, Pham N, Lee C, Jang SH. Int J Mol Sci 20 E1362 (2019)
  52. Glucose-6-Phosphate Dehydrogenase, ZwfA, a Dual Cofactor-Specific Isozyme Is Predominantly Involved in the Glucose Metabolism of Pseudomonas bharatica CSV86T. Shah BA, Kasarlawar ST, Phale PS. Microbiol Spectr 10 e0381822 (2022)
  53. Structural and Kinetic Insights Into the Molecular Basis of Salt Tolerance of the Short-Chain Glucose-6-Phosphate Dehydrogenase From Haloferax volcanii. Fuentes-Ugarte N, Herrera SM, Maturana P, Castro-Fernandez V, Guixé V. Front Microbiol 12 730429 (2021)
  54. Crystal structure of Leishmania donovani glucose 6-phosphate dehydrogenase reveals a unique N-terminal domain. Berneburg I, Rahlfs S, Becker K, Fritz-Wolf K. Commun Biol 5 1353 (2022)


Related citations provided by authors (1)

  1. Site-Directed Mutagenesis to Facilitate X-Ray Structural Studies of Leuconostoc Mesenteroides Glucose 6-Phosphate Dehydrogenase. Adams MJ, Basak AK, Gover S, Rowland P, Levy HR Protein Sci. 2 859- (1993)

Quick links