1dhp Citations

The crystal structure of dihydrodipicolinate synthase from Escherichia coli at 2.5 A resolution.

J. Mol. Biol. 246 227-39 (1995)
Cited: 68 times
EuropePMC logo PMID: 7853400


The crystal structure of dihydrodipicolinate synthase from E. coli was determined by multiple isomorphous replacement methods. The structure was refined at a resolution of 2.5 A and the final R-factor is 19.6% for 32,190 reflections between 10.0 A and 2.5 A and F > 2 sigma (F). The crystallographic asymmetric unit contains two monomers related by approximate 2-fold symmetry. A tetramer with approximate 222 symmetry is built up by crystallographic symmetry. The tetramer is almost planar with no contacts between the subunits related by the non-crystallographic dyad. The active sites are accessible from a wide water-filled channel in the center of the tetramer. The dihydrodipicolinate synthase monomer is composed of two domains. Each polypeptide chain is folded into an 8-fold alpha/beta barrel and a C-terminal alpha-helical domain comprising residues 224 to 292. The fold is similar to that of N-acetylneuraminate lyase. The active site lysine 161 is located in the alpha/beta barrel and has access via two entrances from the C-terminal side of the barrel.

Articles - 1dhp mentioned but not cited (3)

  1. Generic algorithm to predict the speed of translational elongation: implications for protein biogenesis. Zhang G, Ignatova Z. PLoS ONE 4 e5036 (2009)
  2. Crystallization, preliminary X-ray diffraction and structure solution of MosA, a dihydrodipicolinate synthase from Sinorhizobium meliloti L5-30. Leduc YA, Phenix CP, Puttick J, Nienaber K, Palmer DR, Delbaere LT. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62 49-51 (2006)
  3. Characterization of a novel N-acetylneuraminic acid lyase favoring N-acetylneuraminic acid synthesis. Ji W, Sun W, Feng J, Song T, Zhang D, Ouyang P, Gu Z, Xie J. Sci Rep 5 9341 (2015)

Reviews citing this publication (5)

  1. Amino acid biosynthesis: new architectures in allosteric enzymes. Curien G, Biou V, Mas-Droux C, Robert-Genthon M, Ferrer JL, Dumas R. Plant Physiol. Biochem. 46 325-339 (2008)
  2. Fucosyltransferases: structure/function studies. de Vries T, Knegtel RM, Holmes EH, Macher BA. Glycobiology 11 119R-128R (2001)
  3. Bacterial diaminopimelate metabolism as a target for antibiotic design. Cox RJ, Sutherland A, Vederas JC. Bioorg. Med. Chem. 8 843-871 (2000)
  4. Feedback inhibition of dihydrodipicolinate synthase enzymes by L-lysine. Blickling S, Knäblein J. Biol. Chem. 378 207-210 (1997)
  5. Circular permutations of natural protein sequences: structural evidence. Lindqvist Y, Schneider G. Curr. Opin. Struct. Biol. 7 422-427 (1997)

Articles citing this publication (60)

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  4. The crystal structure of three site-directed mutants of Escherichia coli dihydrodipicolinate synthase: further evidence for a catalytic triad. Dobson RC, Valegård K, Gerrard JA. J. Mol. Biol. 338 329-339 (2004)
  5. Structure and mechanism of a sub-family of enzymes related to N-acetylneuraminate lyase. Lawrence MC, Barbosa JA, Smith BJ, Hall NE, Pilling PA, Ooi HC, Marcuccio SM. J. Mol. Biol. 266 381-399 (1997)
  6. Crystal structure of transaldolase B from Escherichia coli suggests a circular permutation of the alpha/beta barrel within the class I aldolase family. Jia J, Huang W, Schörken U, Sahm H, Sprenger GA, Lindqvist Y, Schneider G. Structure 4 715-724 (1996)
  7. Mimicking natural evolution in vitro: an N-acetylneuraminate lyase mutant with an increased dihydrodipicolinate synthase activity. Joerger AC, Mayer S, Fersht AR. Proc. Natl. Acad. Sci. U.S.A. 100 5694-5699 (2003)
  8. Structure of dihydrodipicolinate synthase of Nicotiana sylvestris reveals novel quaternary structure. Blickling S, Beisel HG, Bozic D, Knäblein J, Laber B, Huber R. J. Mol. Biol. 274 608-621 (1997)
  9. Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus. Sood R, Bonner TI, Makalowska I, Stephan DA, Robbins CM, Connors TD, Morgenbesser SD, Su K, Faruque MU, Pinkett H, Graham C, Baxevanis AD, Klinger KW, Landes GM, Trent JM, Carpten JD. Genomics 73 211-222 (2001)
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  11. Crystal structure of dihydrodipicolinate synthase (BA3935) from Bacillus anthracis at 1.94 A resolution. Blagova E, Levdikov V, Milioti N, Fogg MJ, Kalliomaa AK, Brannigan JA, Wilson KS, Wilkinson AJ. Proteins 62 297-301 (2006)
  12. Dihydrodipicolinate synthase from Thermotoga maritima. Pearce FG, Perugini MA, McKerchar HJ, Gerrard JA. Biochem. J. 400 359-366 (2006)
  13. Synthesis and folding of a mirror-image enzyme reveals ambidextrous chaperone activity. Weinstock MT, Jacobsen MT, Kay MS. Proc. Natl. Acad. Sci. U.S.A. 111 11679-11684 (2014)
  14. Insight into the self-association of key enzymes from pathogenic species. Perugini MA, Griffin MD, Smith BJ, Webb LE, Davis AJ, Handman E, Gerrard JA. Eur. Biophys. J. 34 469-476 (2005)
  15. Structural and functional characterization of Staphylococcus aureus dihydrodipicolinate synthase. Girish TS, Sharma E, Gopal B. FEBS Lett. 582 2923-2930 (2008)
  16. Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies. Beck BB, Baasner A, Buescher A, Habbig S, Reintjes N, Kemper MJ, Sikora P, Mache C, Pohl M, Stahl M, Toenshoff B, Pape L, Fehrenbach H, Jacob DE, Grohe B, Wolf MT, Nürnberg G, Yigit G, Salido EC, Hoppe B. Eur. J. Hum. Genet. 21 162-172 (2013)
  17. Dihydrodipicolinate synthase (DHDPS) from Escherichia coli displays partial mixed inhibition with respect to its first substrate, pyruvate. Dobson RC, Griffin MD, Roberts SJ, Gerrard JA. Biochimie 86 311-315 (2004)
  18. Single-amino acid substitutions eliminate lysine inhibition of maize dihydrodipicolinate synthase. Shaver JM, Bittel DC, Sellner JM, Frisch DA, Somers DA, Gengenbach BG. Proc. Natl. Acad. Sci. U.S.A. 93 1962-1966 (1996)
  19. KiDoQ: using docking based energy scores to develop ligand based model for predicting antibacterials. Garg A, Tewari R, Raghava GP. BMC Bioinformatics 11 125 (2010)
  20. Overproduction of L-Lysine from methanol by Methylobacillus glycogenes derivatives carrying a plasmid with a mutated dapA gene. Motoyama H, Yano H, Terasaki Y, Anazawa H. Appl. Environ. Microbiol. 67 3064-3070 (2001)
  21. Characterization and crystal structure of lysine insensitive Corynebacterium glutamicum dihydrodipicolinate synthase (cDHDPS) protein. Rice EA, Bannon GA, Glenn KC, Jeong SS, Sturman EJ, Rydel TJ. Arch. Biochem. Biophys. 480 111-121 (2008)
  22. Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel adolase class. Bauer S, Schott AK, Illarionova V, Bacher A, Huber R, Fischer M. J. Mol. Biol. 339 967-979 (2004)
  23. Heterocyclic inhibitors of dihydrodipicolinate synthase are not competitive. Turner JJ, Gerrard JA, Hutton CA. Bioorg. Med. Chem. 13 2133-2140 (2005)
  24. Exploring the dihydrodipicolinate synthase tetramer: how resilient is the dimer-dimer interface? Griffin MD, Dobson RC, Gerrard JA, Perugini MA. Arch. Biochem. Biophys. 494 58-63 (2010)
  25. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DapA (Rv2753c) from Mycobacterium tuberculosis. Kefala G, Weiss MS. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62 1116-1119 (2006)
  26. Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology? Janecek S. Protein Sci. 5 1136-1143 (1996)
  27. Crystal, solution and in silico structural studies of dihydrodipicolinate synthase from the common grapevine. Atkinson SC, Dogovski C, Downton MT, Pearce FG, Reboul CF, Buckle AM, Gerrard JA, Dobson RC, Wagner J, Perugini MA. PLoS ONE 7 e38318 (2012)
  28. How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase? Soares da Costa TP, Muscroft-Taylor AC, Dobson RC, Devenish SR, Jameson GB, Gerrard JA. Biochimie 92 837-845 (2010)
  29. Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues. Boughton BA, Griffin MD, O'Donnell PA, Dobson RC, Perugini MA, Gerrard JA, Hutton CA. Bioorg. Med. Chem. 16 9975-9983 (2008)
  30. Conserved main-chain peptide distortions: a proposed role for Ile203 in catalysis by dihydrodipicolinate synthase. Dobson RC, Griffin MD, Devenish SR, Pearce FG, Hutton CA, Gerrard JA, Jameson GB, Perugini MA. Protein Sci. 17 2080-2090 (2008)
  31. Virtual Screening of potential drug-like inhibitors against Lysine/DAP pathway of Mycobacterium tuberculosis. Garg A, Tewari R, Raghava GP. BMC Bioinformatics 11 Suppl 1 S53 (2010)
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  33. Structural and dynamic requirements for optimal activity of the essential bacterial enzyme dihydrodipicolinate synthase. Reboul CF, Porebski BT, Griffin MD, Dobson RC, Perugini MA, Gerrard JA, Buckle AM. PLoS Comput. Biol. 8 e1002537 (2012)
  34. The C-terminal domain of Escherichia coli dihydrodipicolinate synthase (DHDPS) is essential for maintenance of quaternary structure and efficient catalysis. Guo BB, Devenish SR, Dobson RC, Muscroft-Taylor AC, Gerrard JA. Biochem. Biophys. Res. Commun. 380 802-806 (2009)
  35. Purification, crystallization and preliminary X-ray diffraction studies to near-atomic resolution of dihydrodipicolinate synthase from methicillin-resistant Staphylococcus aureus. Burgess BR, Dobson RC, Dogovski C, Jameson GB, Parker MW, Perugini MA. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 659-661 (2008)
  36. MosA, a protein implicated in rhizopine biosynthesis in Sinorhizobium meliloti L5-30, is a dihydrodipicolinate synthase. Tam PH, Phenix CP, Palmer DR. J. Mol. Biol. 335 393-397 (2004)
  37. Cloning of Lactobacillus plantarum IAM 12477 lysine biosynthetic genes encoding functional aspartate semialdehyde dehydrogenase, dihydrodipicolinate synthase, and dihydrodipicolinate reductase Cahyanto MN, Kawasaki H, Fujiyama K, Seki T. World J. Microbiol. Biotechnol. 22 409-416 (2006)
  38. A molecule-centered method for accelerating the calculation of hydrodynamic interactions in Brownian dynamics simulations containing many flexible biomolecules. Elcock AH. J Chem Theory Comput 9 3224-3239 (2013)
  39. The enzyme 4-hydroxy-2-oxoglutarate aldolase is deficient in primary hyperoxaluria type III. Hoppe B. Nephrol. Dial. Transplant. 27 3024-3026 (2012)
  40. A tetrameric structure is not essential for activity in dihydrodipicolinate synthase (DHDPS) from Mycobacterium tuberculosis. Evans G, Schuldt L, Griffin MD, Devenish SR, Grant Pearce F, Perugini MA, Dobson RC, Jameson GB, Weiss MS, Gerrard JA. Arch. Biochem. Biophys. 512 154-159 (2011)
  41. Structure of dihydrodipicolinate synthase from Methanocaldococcus jannaschii. Padmanabhan B, Strange RW, Antonyuk SV, Ellis MJ, Hasnain SS, Iino H, Agari Y, Bessho Y, Yokoyama S. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 65 1222-1226 (2009)
  42. The purification, crystallization and preliminary X-ray diffraction analysis of dihydrodipicolinate synthase from Clostridium botulinum. Dobson RC, Atkinson SC, Gorman MA, Newman JM, Parker MW, Perugini MA. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 206-208 (2008)
  43. The high-resolution structure of dihydrodipicolinate synthase from Escherichia coli bound to its first substrate, pyruvate. Devenish SR, Gerrard JA, Jameson GB, Dobson RC. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 1092-1095 (2008)
  44. Structural, kinetic and computational investigation of Vitis vinifera DHDPS reveals new insight into the mechanism of lysine-mediated allosteric inhibition. Atkinson SC, Dogovski C, Downton MT, Czabotar PE, Dobson RC, Gerrard JA, Wagner J, Perugini MA. Plant Mol. Biol. 81 431-446 (2013)
  45. Tetrahydrodipicolinate N-succinyltransferase and dihydrodipicolinate synthase from Pseudomonas aeruginosa: structure analysis and gene deletion. Schnell R, Oehlmann W, Sandalova T, Braun Y, Huck C, Maringer M, Singh M, Schneider G. PLoS ONE 7 e31133 (2012)
  46. Proteomics of early and late cold shock stress on thermophilic bacterium, Thermus sp. GH5. Yousefi-Nejad M, Manesh HN, Khajeh K. J Proteomics 74 2100-2111 (2011)
  47. L-Hydroxyproline and d-Proline Catabolism in Sinorhizobium meliloti. Chen S, White CE, diCenzo GC, Zhang Y, Stogios PJ, Savchenko A, Finan TM. J. Bacteriol. 198 1171-1181 (2016)
  48. Decoding Structural Properties of a Partially Unfolded Protein Substrate: En Route to Chaperone Binding. Nagpal S, Tiwari S, Mapa K, Thukral L. PLoS Comput. Biol. 11 e1004496 (2015)
  49. Identification of the bona fide DHDPS from a common plant pathogen. Atkinson SC, Hor L, Dogovski C, Dobson RC, Perugini MA. Proteins 82 1869-1883 (2014)
  50. Medicago truncatula dihydrodipicolinate synthase (DHDPS) enzymes display novel regulatory properties. Erzeel E, Van Bochaute P, Thu TT, Angenon G. Plant Mol. Biol. 81 401-415 (2013)
  51. Crystal structure of YagE, a putative DHDPS-like protein from Escherichia coli K12. Manicka S, Peleg Y, Unger T, Albeck S, Dym O, Greenblatt HM, Bourenkov G, Lamzin V, Krishnaswamy S, Sussman JL. Proteins 71 2102-2108 (2008)
  52. Preliminary crystallographic analysis of L-2-keto-3-deoxyarabonate dehydratase, an enzyme involved in an alternative bacterial pathway of L-arabinose metabolism. Shimada N, Mikami B, Watanabe S, Makino K. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 63 393-395 (2007)
  53. Cloning, expression, purification and crystallization of dihydrodipicolinate synthase from the psychrophile Shewanella benthica. Wubben JM, Dogovski C, Dobson RC, Codd R, Gerrard JA, Parker MW, Perugini MA. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 66 1511-1516 (2010)
  54. Crystal structure and in silico studies of dihydrodipicolinate synthase (DHDPS) from Aquifex aeolicus. Sridharan U, Ebihara A, Kuramitsu S, Yokoyama S, Kumarevel T, Ponnuraj K. Extremophiles 18 973-985 (2014)
  55. Cloning, expression, purification, crystallization and X-ray diffraction analysis of dihydrodipicolinate synthase from the human pathogenic bacterium Bartonella henselae strain Houston-1 at 2.1 Å resolution. Naqvi KF, Staker BL, Dobson RC, Serbzhinskiy D, Sankaran B, Myler PJ, Hudson AO. Acta Crystallogr F Struct Biol Commun 72 2-9 (2016)
  56. Dynamic Modelling Reveals 'Hotspots' on the Pathway to Enzyme-Substrate Complex Formation. Gordon SE, Weber DK, Downton MT, Wagner J, Perugini MA. PLoS Comput. Biol. 12 e1004811 (2016)
  57. Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues. Shrivastava P, Navratna V, Silla Y, Dewangan RP, Pramanik A, Chaudhary S, Rayasam G, Kumar A, Gopal B, Ramachandran S. Sci Rep 6 30827 (2016)
  58. Structure and Function of Cyanobacterial DHDPS and DHDPR. Christensen JB, Soares da Costa TP, Faou P, Pearce FG, Panjikar S, Perugini MA. Sci Rep 6 37111 (2016)
  59. Letter Structure and inhibition of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus. North RA, Watson AJ, Pearce FG, Muscroft-Taylor AC, Friemann R, Fairbanks AJ, Dobson RC. FEBS Lett. 590 4414-4428 (2016)
  60. A Metagenomic Analysis of Bacterial Microbiota in the Digestive Tract of Triatomines. Carels N, Gumiel M, da Mota FF, de Carvalho Moreira CJ, Azambuja P. Bioinform Biol Insights 11 1177932217733422 (2017)

Related citations provided by authors (1)

  1. Escherichia Coli Dihydrodipicolinate Synthase. Identification of the Active Site and Crystallization. Laber B, Gomis-Ruth FX, Romao MJ, Huber R Biochem. J. 288 691- (1992)