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Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis.

Hadfield A, Kryger G, Ouyang J, Petsko GA, Ringe D, Viola R
J Mol Biol 289 991-1002 (1999)
Cited: 38 times
EuropePMC logo PMID: 10369777

Abstract

Aspartate beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point in an essential aspartic biosynthetic pathway found in bacteria, fungi and the higher plants. Mutations in the asd gene encoding for ASADH that produce an inactive enzyme are lethal, which suggests that ASADH may be an effective target for antibacterial, herbicidal and fungicidal agents. We have solved the crystal structure of the Escherichia coli enzyme to 2.5 A resolution using single isomorphous replacement and 3-fold non-crystallographic symmetry. Each monomer has an N-terminal nucleotide-binding domain and a dimerisation domain. The presence of an essential cysteine locates the active site in a cleft between the two domains. The functional dimer has the appearance of a butterfly, with the NADP-binding domains forming the wings and the dimerisation domain forming the body.A histidine residue is identified as a likely acid/base catalyst in the enzymic reaction. Other amino acids implicated in the enzymic activity by mutagenesis are found in the active site region and define the substrate binding pocket.

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Articles - 1brm mentioned but not cited (5)

  1. Prediction of catalytic residues using Support Vector Machine with selected protein sequence and structural properties. Petrova NV, Wu CH. BMC Bioinformatics 7 312 (2006)
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  4. Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase. Blanco J, Moore RA, Viola RE. Proc Natl Acad Sci U S A 100 12613-12617 (2003)
  5. Purification, crystallization and preliminary X-ray diffraction analysis of aspartate semialdehyde dehydrogenase (Rv3708c) from Mycobacterium tuberculosis. Vyas R, Kumar V, Panjikar S, Karthikeyan S, Kishan KV, Tewari R, Weiss MS. Acta Crystallogr Sect F Struct Biol Cryst Commun 64 167-170 (2008)


Articles citing this publication (32)

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  3. Crystal structure of saccharopine reductase from Magnaporthe grisea, an enzyme of the alpha-aminoadipate pathway of lysine biosynthesis. Johansson E, Steffens JJ, Lindqvist Y, Schneider G. Structure 8 1037-1047 (2000)
  4. A new branch in the family: structure of aspartate-beta-semialdehyde dehydrogenase from Methanococcus jannaschii. Faehnle CR, Ohren JF, Viola RE. J Mol Biol 353 1055-1068 (2005)
  5. High-resolution structures reveal details of domain closure and "half-of-sites-reactivity" in Escherichia coli aspartate beta-semialdehyde dehydrogenase. Nichols CE, Dhaliwal B, Lockyer M, Hawkins AR, Stammers DK. J Mol Biol 341 797-806 (2004)
  6. The crystal structure of d-glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeon Methanothermus fervidus in the presence of NADP(+) at 2.1 A resolution. Charron C, Talfournier F, Isupov MN, Littlechild JA, Branlant G, Vitoux B, Aubry A. J Mol Biol 297 481-500 (2000)
  7. Expression and purification of aspartate beta-semialdehyde dehydrogenase from infectious microorganisms. Moore RA, Bocik WE, Viola RE. Protein Expr Purif 25 189-194 (2002)
  8. Cloning and characterization of aspartate-beta-semialdehyde dehydrogenase from Mycobacterium tuberculosis H37 Rv. Shafiani S, Sharma P, Vohra RM, Tewari R. J Appl Microbiol 98 832-838 (2005)
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  11. Overproduction, purification, and characterization of recombinant aspartate semialdehyde dehydrogenase from Arabidopsis thaliana. Paris S, Wessel PM, Dumas R. Protein Expr Purif 24 99-104 (2002)
  12. Pharmacoinformatics analysis to identify inhibitors of Mtb-ASADH. Kumar R, Garg P, Bharatam PV. J Biomol Struct Dyn 34 1-14 (2016)
  13. Shape-based virtual screening, docking, and molecular dynamics simulations to identify Mtb-ASADH inhibitors. Kumar R, Garg P, Bharatam PV. J Biomol Struct Dyn 33 1082-1093 (2015)
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  16. Molecular Modeling and Active Site Binding Mode Characterization of Aspartate β-Semialdehyde Dehydrogenase Family. Kumar R, Garg P. Mol Inform 32 377-383 (2013)
  17. Crystal structure of putative N-acetyl-gamma-glutamyl-phosphate reductase (AK071544) from rice (Oryza sativa). Nonaka T, Kita A, Miura-Ohnuma J, Katoh E, Inagaki N, Yamazaki T, Miki K. Proteins 61 1137-1140 (2005)
  18. Lysine and Threonine Biosynthesis from Aspartate Contributes to Staphylococcus aureus Growth in Calf Serum. Oogai Y, Yamaguchi M, Kawada-Matsuo M, Sumitomo T, Kawabata S, Komatsuzawa H. Appl Environ Microbiol 82 6150-6157 (2016)
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  20. Mutagenesis of Key Residues in the Binding Center of l-Aspartate-b-Semialdehyde Dehydrogenase from Escherichia coli Enhances Utilization of the Cofactor NAD(H). Xu X, Chen J, Wang Q, Duan C, Li Y, Wang R, Yang S. Chembiochem 17 56-64 (2016)
  21. Synthesis and evaluation of conformationally restricted inhibitors of aspartate semialdehyde dehydrogenase. Evitt AS, Cox RJ. Mol Biosyst 7 1564-1575 (2011)
  22. A cautionary tale of structure-guided inhibitor development against an essential enzyme in the aspartate-biosynthetic pathway. Pavlovsky AG, Thangavelu B, Bhansali P, Viola RE. Acta Crystallogr D Biol Crystallogr 70 3244-3252 (2014)
  23. A new synthesis of phosphoramidates: inhibitors of the key bacterial enzyme aspartate semi-aldehyde dehydrogenase. Adams LA, Cox RJ, Gibson JS, Mayo-Martín MB, Walter M, Whittingham W. Chem Commun (Camb) 2004-2005 (2002)
  24. Mechanism of the dehydrogenase reaction of DmpFG and analysis of inter-subunit channeling efficiency and thermodynamic parameters in the overall reaction. Smith NE, Tie WJ, Flematti GR, Stubbs KA, Corry B, Attwood PV, Vrielink A. Int J Biochem Cell Biol 45 1878-1885 (2013)
  25. iTRAQ-Based Comparative Proteomics Analysis of the Fruiting Dikaryon and the Non-fruiting Monokaryon of Flammulina velutipes. Liu JY, Chang MC, Meng JL, Feng CP, Liu YN. Curr Microbiol 74 114-124 (2017)
  26. Improved expression, purification and crystallization of a putative N-acetyl-gamma-glutamyl-phosphate reductase from rice (Oryza sativa). Miura-Ohnuma J, Nonaka T, Katoh S, Murata K, Kita A, Miki K, Katoh E. Acta Crystallogr Sect F Struct Biol Cryst Commun 61 1058-1061 (2005)
  27. Investigation of microbial community interactions between Lake Washington methanotrophs using -------genome-scale metabolic modeling. Islam MM, Le T, Daggumati SR, Saha R. PeerJ 8 e9464 (2020)
  28. Structural Insights into the Tetrameric State of Aspartate-β-semialdehyde Dehydrogenases from Fungal Species. Li Q, Mu Z, Zhao R, Dahal G, Viola RE, Liu T, Jin Q, Cui S. Sci Rep 6 21067 (2016)
  29. Characterizing the Mechanisms of Metalaxyl, Bronopol and Copper Sulfate against Saprolegnia parasitica Using Modern Transcriptomics. Wang Y, Wu H, Fei S, Zhang J, Hu K. Genes (Basel) 13 1524 (2022)
  30. Comparison on extreme pathways reveals nature of different biological processes. Xi Y, Zhao Y, Wang L, Wang F. BMC Syst Biol 8 Suppl 1 S10 (2014)
  31. Engineer a double team of short-lived and glucose-sensing bacteria for cancer eradication. Jin Y, Fu L. Cell Rep Med 4 101043 (2023)
  32. Structural characterization of aspartate-semialdehyde dehydrogenase from Pseudomonas aeruginosa and Neisseria gonorrhoeae. Teakel SL, Fairman JW, Muruthi MM, Abendroth J, Dranow DM, Lorimer DD, Myler PJ, Edwards TE, Forwood JK. Sci Rep 12 14010 (2022)


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