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Structural studies of domain movement in active-site mutants of porphobilinogen deaminase from Bacillus megaterium.

Guo J, Erskine P, Coker AR, Wood SP, Cooper JB
Acta Crystallogr F Struct Biol Commun 73 612-620 (2017)
Related entries: 5ov4, 5ov5

Cited: 8 times
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Abstract

The enzyme porphobilinogen deaminase (PBGD) is one of the key enzymes in tetrapyrrole biosynthesis. It catalyses the formation of a linear tetrapyrrole from four molecules of the substrate porphobilinogen (PBG). It has a dipyrromethane cofactor (DPM) in the active site which is covalently linked to a conserved cysteine residue through a thioether bridge. The substrate molecules are linked to the cofactor in a stepwise head-to-tail manner during the reaction, which is catalysed by a conserved aspartate residue: Asp82 in the B. megaterium enzyme. Three mutations have been made affecting Asp82 (D82A, D82E and D82N) and their crystal structures have been determined at resolutions of 2.7, 1.8 and 1.9 Å, respectively. These structures reveal that whilst the D82E mutant possesses the DPM cofactor, in the D82N and D82A mutants the cofactor is likely to be missing, incompletely assembled or disordered. Comparison of the mutant PBGD structures with that of the wild-type enzyme shows that there are significant domain movements and suggests that the enzyme adopts `open' and `closed' conformations, potentially in response to substrate binding.

Reviews - 5ov6 mentioned but not cited (1)

  1. Acute Intermittent Porphyria: An Overview of Therapy Developments and Future Perspectives Focusing on Stabilisation of HMBS and Proteostasis Regulators. Bustad HJ, Kallio JP, Vorland M, Fiorentino V, Sandberg S, Schmitt C, Aarsand AK, Martinez A. Int J Mol Sci 22 E675 (2021)

Articles - 5ov6 mentioned but not cited (3)

  1. Structural studies of domain movement in active-site mutants of porphobilinogen deaminase from Bacillus megaterium. Guo J, Erskine P, Coker AR, Wood SP, Cooper JB. Acta Crystallogr F Struct Biol Commun 73 612-620 (2017)
  2. The structure of Escherichia coli ExoIX--implications for DNA binding and catalysis in flap endonucleases. Anstey-Gilbert CS, Hemsworth GR, Flemming CS, Hodskinson MR, Zhang J, Sedelnikova SE, Stillman TJ, Sayers JR, Artymiuk PJ. Nucleic Acids Res 41 8357-8367 (2013)
  3. The crystal structures of the enzyme hydroxymethylbilane synthase, also known as porphobilinogen deaminase. Helliwell JR. Acta Crystallogr F Struct Biol Commun 77 388-398 (2021)


Articles citing this publication (4)

  1. Human hydroxymethylbilane synthase: Molecular dynamics of the pyrrole chain elongation identifies step-specific residues that cause AIP. Bung N, Roy A, Chen B, Das D, Pradhan M, Yasuda M, New MI, Desnick RJ, Bulusu G. Proc Natl Acad Sci U S A 115 E4071-E4080 (2018)
  2. Isolation and Identification of Antibacterial Bioactive Compounds From Bacillus megaterium L2. Xie Y, Peng Q, Ji Y, Xie A, Yang L, Mu S, Li Z, He T, Xiao Y, Zhao J, Zhang Q. Front Microbiol 12 645484 (2021)
  3. Manually curated genome-scale reconstruction of the metabolic network of Bacillus megaterium DSM319. Aminian-Dehkordi J, Mousavi SM, Jafari A, Mijakovic I, Marashi SA. Sci Rep 9 18762 (2019)
  4. Computational modeling of the catalytic mechanism of hydroxymethylbilane synthase. Bung N, Roy A, Priyakumar UD, Bulusu G. Phys Chem Chem Phys 21 7932-7940 (2019)


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