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High resolution crystal structure of a Mg2+-dependent porphobilinogen synthase.

Frankenberg N, Erskine PT, Cooper JB, Shoolingin-Jordan PM, Jahn D, Heinz DW
J Mol Biol 289 591-602 (1999)
Cited: 44 times
EuropePMC logo PMID: 10356331

Abstract

Common to the biosynthesis of all known tetrapyrroles is the condensation of two molecules of 5-aminolevulinic acid to the pyrrole porphobilinogen catalyzed by the enzyme porphobilinogen synthase (PBGS). Two major classes of PBGS are known. Zn2+-dependent PBGSs are found in mammals, yeast and some bacteria including Escherichia coli, while Mg2+-dependent PBGSs are present mainly in plants and other bacteria. The crystal structure of the Mg2+-dependent PBGS from the human pathogen Pseudomonas aeruginosa in complex with the competitive inhibitor levulinic acid (LA) solved at 1.67 A resolution shows a homooctameric enzyme that consists of four asymmetric dimers. The monomers in each dimer differ from each other by having a "closed" and an "open" active site pocket. In the closed subunit, the active site is completely shielded from solvent by a well-defined lid that is partially disordered in the open subunit. A single molecule of LA binds to a mainly hydrophobic pocket in each monomer where it is covalently attached via a Schiff base to an active site lysine residue. Whereas no metal ions are found in the active site of both monomers, a single well-defined and highly hydrated Mg2+is present only in the closed form about 14 A away from the Schiff base forming nitrogen atom of the active site lysine. We conclude that the observed differences in the active sites of both monomers might be induced by Mg2+-binding to this remote site and propose a structure-based mechanism for this allosteric Mg2+in rate enhancement.

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  2. The biochemistry of heme biosynthesis. Heinemann IU, Jahn M, Jahn D. Arch Biochem Biophys 474 238-251 (2008)
  3. Structure and function of enzymes in heme biosynthesis. Layer G, Reichelt J, Jahn D, Heinz DW. Protein Sci 19 1137-1161 (2010)
  4. Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product. Dailey HA, Dailey TA, Gerdes S, Jahn D, Jahn M, O'Brian MR, Warren MJ. Microbiol Mol Biol Rev 81 e00048-16 (2017)
  5. The porphobilinogen synthase catalyzed reaction mechanism. Jaffe EK. Bioorg Chem 32 316-325 (2004)
  6. Allostery and the dynamic oligomerization of porphobilinogen synthase. Jaffe EK, Lawrence SH. Arch Biochem Biophys 519 144-153 (2012)
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  2. Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase. Breinig S, Kervinen J, Stith L, Wasson AS, Fairman R, Wlodawer A, Zdanov A, Jaffe EK. Nat Struct Biol 10 757-763 (2003)
  3. Shape shifting leads to small-molecule allosteric drug discovery. Lawrence SH, Ramirez UD, Tang L, Fazliyez F, Kundrat L, Markham GD, Jaffe EK. Chem Biol 15 586-596 (2008)
  4. An unusual phylogenetic variation in the metal ion binding sites of porphobilinogen synthase. Jaffe EK. Chem Biol 10 25-34 (2003)
  5. Synergistic substrate inhibition of ent-copalyl diphosphate synthase: a potential feed-forward inhibition mechanism limiting gibberellin metabolism. Prisic S, Peters RJ. Plant Physiol 144 445-454 (2007)
  6. Delta-aminolevulinic acid dehydratase from Plasmodium falciparum: indigenous versus imported. Dhanasekaran S, Chandra NR, Chandrasekhar Sagar BK, Rangarajan PN, Padmanaban G. J Biol Chem 279 6934-6942 (2004)
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  8. Recent advances in the biosynthesis of modified tetrapyrroles: the discovery of an alternative pathway for the formation of heme and heme d 1. Bali S, Palmer DJ, Schroeder S, Ferguson SJ, Warren MJ. Cell Mol Life Sci 71 2837-2863 (2014)
  9. Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism. Frère F, Schubert WD, Stauffer F, Frankenberg N, Neier R, Jahn D, Heinz DW. J Mol Biol 320 237-247 (2002)
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  14. Inhibition of Escherichia coli porphobilinogen synthase using analogs of postulated intermediates. Jarret C, Stauffer F, Henz ME, Marty M, Lüönd RM, Bobálová J, Schürmann P, Neier R. Chem Biol 7 185-196 (2000)
  15. Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion independent hexamer. Bollivar DW, Clauson C, Lighthall R, Forbes S, Kokona B, Fairman R, Kundrat L, Jaffe EK. BMC Biochem 5 17 (2004)
  16. The Remarkable Character of Porphobilinogen Synthase. Jaffe EK. Acc Chem Res 49 2509-2517 (2016)
  17. Probing the oligomeric assemblies of pea porphobilinogen synthase by analytical ultracentrifugation. Kokona B, Rigotti DJ, Wasson AS, Lawrence SH, Jaffe EK, Fairman R. Biochemistry 47 10649-10656 (2008)
  18. Structural studies of substrate and product complexes of 5-aminolaevulinic acid dehydratase from humans, Escherichia coli and the hyperthermophile Pyrobaculum calidifontis. Mills-Davies N, Butler D, Norton E, Thompson D, Sarwar M, Guo J, Gill R, Azim N, Coker A, Wood SP, Erskine PT, Coates L, Cooper JB, Rashid N, Akhtar M, Shoolingin-Jordan PM. Acta Crystallogr D Struct Biol 73 9-21 (2017)
  19. Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin. Heinemann IU, Schulz C, Schubert WD, Heinz DW, Wang YG, Kobayashi Y, Awa Y, Wachi M, Jahn D, Jahn M. Antimicrob Agents Chemother 54 267-272 (2010)
  20. X-ray structure of a putative reaction intermediate of 5-aminolaevulinic acid dehydratase. Erskine PT, Coates L, Butler D, Youell JH, Brindley AA, Wood SP, Warren MJ, Shoolingin-Jordan PM, Cooper JB. Biochem J 373 733-738 (2003)
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  23. Pseudomonas aeruginosa porphobilinogen synthase assembly state regulators: hit discovery and initial SAR studies. Reitz AB, Ramirez UD, Stith L, Du Y, Smith GR, Jaffe EK. ARKIVOC 2010 175-188 (2010)
  24. The activation mechanism of human porphobilinogen synthase by 2-mercaptoethanol: intrasubunit transfer of a reserve zinc ion and coordination with three cysteines in the active center. Sawada N, Nagahara N, Sakai T, Nakajima Y, Minami M, Kawada T. J Biol Inorg Chem 10 199-207 (2005)
  25. Site-directed mutagenesis of rice serine racemase: evidence that Glu219 and Asp225 mediate the effects of Mg2+ on the activity. Gogami Y, Kobayashi A, Ikeuchi T, Oikawa T. Chem Biodivers 7 1579-1590 (2010)
  26. Tracking the evolution of porphobilinogen synthase metal dependence in vitro. Frère F, Reents H, Schubert WD, Heinz DW, Jahn D. J Mol Biol 345 1059-1070 (2005)
  27. Inhibition studies of porphobilinogen synthase from Escherichia coli differentiating between the two recognition sites. Stauffer F, Zizzari E, Engeloch-Jarret C, Faurite JP, Bobálová J, Neier R. Chembiochem 2 343-354 (2001)
  28. Synthesis of bisubstrate inhibitors of porphobilinogen synthase from Pseudomonas aeruginosa. Gacond S, Frère F, Nentwich M, Faurite JP, Frankenberg-Dinkel N, Neier R. Chem Biodivers 4 189-202 (2007)
  29. Towards Initial Indications for a Thiol-Based Redox Control of Arabidopsis 5-Aminolevulinic Acid Dehydratase. Wittmann D, Kløve S, Wang P, Grimm B. Antioxidants (Basel) 7 E152 (2018)
  30. wALADin benzimidazoles differentially modulate the function of porphobilinogen synthase orthologs. Lentz CS, Halls VS, Hannam JS, Strassel S, Lawrence SH, Jaffe EK, Famulok M, Hoerauf A, Pfarr KM. J Med Chem 57 2498-2510 (2014)
  31. Molecular evolution of multiple-level control of heme biosynthesis pathway in animal kingdom. Tzou WS, Chu Y, Lin TY, Hu CH, Pai TW, Liu HF, Lin HJ, Cases I, Rojas A, Sanchez M, You ZY, Hsu MW. PLoS One 9 e86718 (2014)
  32. Probing the active site of rat porphobilinogen synthase using newly developed inhibitors. Li N, Chu X, Liu X, Li D. Bioorg Chem 37 33-40 (2009)
  33. Synthesis and antibacterial activity of alaremycin derivatives for the porphobilinogen synthase. Iwai N, Nakayama K, Oku J, Kitazume T. Bioorg Med Chem Lett 21 2812-2815 (2011)
  34. Biochemical and molecular characterization of a novel porphobilinogen synthase from Corynebacterium glutamicum. Zhu D, Wu C, Niu C, Li H, Ge F, Li W. World J Microbiol Biotechnol 39 165 (2023)


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