Protein Crystallography and Drug Design

  • W. G. J. Hol
Conference paper
Part of the Bayer AG Centenary Symposium book series (BAYER)

Abstract

Safe and reliable drugs belong to the most impressive scientific achievements of mankind. One wishes only that there were more drugs such as penicillin, which allows recovery from serious and painful bacterial infections in a matter of days, if not hours. Unfortunately, the discovery of such compounds with almost miraculous curing properties is a very rare event, indeed.

Keywords

Manifold Penicillin Methotrexate Folate NADPH 

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References

  1. 1.
    Hol WGJ (1986) Protein crystallography and rational drug design. Angew Chemie 25: 767–778CrossRefGoogle Scholar
  2. 2.
    Amit AG, Mariuzza RA, Phillips SEV, Poljak RJ (1985) Three-dimensional structure of an antigen-antibody complex at 6 Å resolution. Nature 313: 156–158PubMedCrossRefGoogle Scholar
  3. 3.
    Colman PM, Laver WG, Varghese JN, Baker AT, Tulloch PA, Air GM, Webster RG (1987) Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature 326: 358–363PubMedCrossRefGoogle Scholar
  4. 4.
    Riechmann L, Clark M, Waldmann H, Winter G (1988) Reshaping human antibodies therapy. Nature 332: 323–327PubMedCrossRefGoogle Scholar
  5. 5.
    Shaanan B (1983) Structure of human oxyhaemoglobin at 2.1 Å resolution. J Mol Biol 171: 31–59PubMedCrossRefGoogle Scholar
  6. 6.
    Fermi G, Perutz MF, Shaanan B, Fourme R (1984) The crystal structure of human deoxyhaemoglobin at 1.74 Å resolution. J Mol Biol 175: 159–174PubMedCrossRefGoogle Scholar
  7. 7.
    Goodford P (1977) The haemoglobin molecule as a model drug receptor. In: Roberts GKC (ed) Drug action at the molecular level. Macmillan, London, pp 109–126Google Scholar
  8. 8.
    Walder JA, Walder RY, Arnone A (1980) Development of antisickling compounds that chemically modify hemoglobin S specifically within the 2,3-diphosphoglycerate binding site. J. Mol Biol 141: 195–216PubMedCrossRefGoogle Scholar
  9. 9.
    Abraham DJ, Perutz MF, Phillips SEV (1983) Physiological and X-raystudies of potential antisickling agents. Proc Natl Acad Sci 80: 324–328PubMedCrossRefGoogle Scholar
  10. 10.
    Cushman DW, Cheung HS, Sabo EF, Ondetti MA (1977) Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry 16: 5484–5491PubMedCrossRefGoogle Scholar
  11. 11.
    Navia MA, Springer JP, Poe M, Boger J, Hoogsteen K (1984) Preliminary X-ray crystallographic data on mouse submaxillary gland renin and renin-inhibitor complexes. J Biol Chem 259: 12714–12717PubMedGoogle Scholar
  12. 12.
    Sibanda BL, Blundell T, Hobart PM, Fogliano M, Bindra JS, Dominy BW, Chirgwin JM (1984) Computer graphics modelling of human renin. Specificity, catalytic activity and intron-exon junctions. FEBS Lett 174: 102–111PubMedCrossRefGoogle Scholar
  13. 13.
    Bolin JT, Filman DJ, Matthews DA, Hamlin RC, Kraut J (1982) Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 Å resolution. J Biol Chem 257: 13650–13662PubMedGoogle Scholar
  14. 14.
    Oefner C, D’Arcy A, Winkler FK (1988) Crystal structure of human dihydrofolate reductase complex with folate. Eur J Biochem 174: 377–385PubMedCrossRefGoogle Scholar
  15. 15.
    Tabin CJ, Bradley SM, Bargmann CI, Weinberg RA, Papageorge AG, Scolnick EM, Dhar R, Lowy DR, Chang EH (1982) Mechanism of activation of a human oncogene. Nature 300: 143–149PubMedCrossRefGoogle Scholar
  16. 16.
    Reddy EP, Reynolds RK, Santos E, Barbacid M (1982) A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature 300: 149–152PubMedCrossRefGoogle Scholar
  17. 17.
    Taparowsky E, Suard Y, Fasano O, Shimizu K, Goldfarb M, Wigler M (1982) Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature 300: 762–765PubMedCrossRefGoogle Scholar
  18. 18.
    Wierenga RK, Hol WGJ (1983) Predicted nucleotide-binding properties of p21 protein and its cancer-associated variant. Nature 302: 842–844PubMedCrossRefGoogle Scholar
  19. 19.
    Hol WGJ, Wierenga RK (1984) The a-helix dipole and the binding of phosphate groups of coenzymes and substrates by proteins. In: Horn AS, de Ranter CJ (eds) X-ray crystallography and drug action. Clarendon, Oxford, pp 151–168Google Scholar
  20. 20.
    de Vos AM, Tong L, Milburn MV, Matias PM, Jancarik J, Noguchi S, Nishimura S, Miura K, Ohtsuka E, Kim SH (1988) Three-dimensional structure of an oncogene protein: catalytic domain of human c-H-ras p21. Science 239: 888–893PubMedCrossRefGoogle Scholar
  21. 21.
    Samuelsson B (1983) Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 220: 568–575PubMedCrossRefGoogle Scholar
  22. 22.
    Dijkstra BW, Kalk KH, Hol WGJ, Drenth J (1981) Structure of bovine pancreatic phospholipase A2 at 1.7 Å resolution. J Mol Biol 147: 97–123PubMedCrossRefGoogle Scholar
  23. 23.
    Dijkstra BW, van Nes GJH, Kalk KH, Brandenburg NP, Hol WGJ, Drenth H (1982) The structure of bovine pancreatic prophospholipase A2 at 3.0 Å resolution. Acta Cryst B38: 793–799CrossRefGoogle Scholar
  24. 24.
    Dijkstra BW, Renetseder R, Kalk KH, Hol WGJ, Drenth J (1983) Structure of porcine pancreatic phospholipase A2 at 2.6 Å resolution and comparison with bovine phospholipase A2. J Mol Biol 168: 163–179PubMedCrossRefGoogle Scholar
  25. 25.
    Okamoto M, Ono T, Tojo H, Yamano T (1985) Immunochemical relatedness between secretory phospholipase A2 and intracellular phospholipase A2. Biochem Biophys Res Comm 128: 788–794PubMedCrossRefGoogle Scholar
  26. 26.
    Dideberg O, Charlier P, Dive G, Joris B, Frère JM, Ghuysen JM (1982) Structure of a Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase at 2.5 Å resolution. Nature 299: 469–470PubMedCrossRefGoogle Scholar
  27. 27.
    Kelly JA, Knox JR, Moews PC, Hite GJ, Bartolone JB, Zhao H, Joris B, Frère JM, Ghuysen JM (1985) 2.8 Å structure of penicillin-sensitive D-alanyl carboxypeptidasetranspeptidase from Streptomyces R61 and complexes with β-lactams. J Biol Chem 260: 6449–6458PubMedGoogle Scholar
  28. 28.
    Herzberg O, Moult J (1987) Bacterial resistance to β-lactam antibodies: Crystal structure of β-lactamase from Staphylococcus aureus PC1 at 2.5 Å resolution.. Science 236: 694–701PubMedCrossRefGoogle Scholar
  29. 29.
    Rossmann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht HJ, Jhnson JE, Kamen G, Luo M, Mosser AG, Rueckert RR, Sherry B, Vriend G (1985) Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317: 145–153PubMedCrossRefGoogle Scholar
  30. 30.
    Hogle JM, Chow M, Filman DJ (1985) Three-dimensional structure of poliovirus at 2.9 Å resolution. Science 229: 1358–1365PubMedCrossRefGoogle Scholar
  31. 31.
    Wilson IA, Shekel JJ, Wiley DC (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature: 289: 366–373PubMedCrossRefGoogle Scholar
  32. 32.
    Varghese JN, Laver WG, Colman PM (1983) Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution. Nature 303: 35–40PubMedCrossRefGoogle Scholar
  33. 33.
    Middlebrook JL, Dorland RB (1984) Bacterial toxins: Cellular mechanisms of action. Microbiol Rev 48: 199–221PubMedGoogle Scholar
  34. 34.
    Sigler PB, Druyan ME, Kiefer HC, Finkelstein RA (1977) Cholera toxin crystals suitable for X-ray diffraction. Science 197: 1277–1279PubMedCrossRefGoogle Scholar
  35. 35.
    Pronk SE, Hofstra H, Gorendijk H, Kingma J, Swarte MBA, Dorner F, Drenth J, Hol WGJ, Witholt B (1985) Heat-labile enterotoxin of Escherichia coli: characterisation of different crystal forms. J Biol Chem 260: 13580–13585PubMedGoogle Scholar
  36. 36.
    Volz KW, Matthews DA, Alden RA, Freer ST, Hansch C, Kaufman BT, Kraut J (1982) Crystal structure of avian dihydrofolate reductase containing phenyltriazine and NADPH. J Biol Chem 257: 2528–2536PubMedGoogle Scholar
  37. 37.
    Filman DJ, Bolin JT, Matthews DA, Kraut J (1982) Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 Å resolution II. Environment of bound NADPH and implications for catalysis. J Biol Chem 257: 13663–13672PubMedGoogle Scholar
  38. 38.
    Matthews DA, Bolin JT, Burridge JM, Filman DJ, Volz KW, Kraut J (1985) Refined crystal structures of Escherichia coli and chicken liver dihydrofolate reductase containing bound trimethoprim. J Biol Chem 260: 381–391PubMedGoogle Scholar
  39. 39.
    Matthews DA, Bolin JT, Burridge JM, Filman DJ, Volz KW, Kraut J (1985) Dihydrofolate reductase. The stereochemistry of inhibitor selectivity. J Biol Chem 260: 392–399PubMedGoogle Scholar
  40. 40.
    Hardy LW, Finer-Moore JS, Montfort WR, Jones MO, Santi DV, Stroud RM (1987) Atomic structure of thymidylate synthase: Target for rational drug design. Science 235: 448–455PubMedCrossRefGoogle Scholar
  41. 41.
    Wierenga RK, Kalk KH, Hol WGJ (1987) Structure determination of the glycosomal triosephosphate isomerase from Trypanosoma brucei brucei at 2.4 Å resolution. J Mol Biol 198: 109–121PubMedCrossRefGoogle Scholar
  42. 42.
    Read RJ, Wierenga RK, Groendijk H, Lambeir A, Opperdoes FR, Hol WGJ (1987) Preliminary crystallographic studies of glycosomal glyceraldehyde phosphate dehydrogenase from Trypanosoma brucei brucei. J Mol Biol 194: 573–575PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • W. G. J. Hol
    • 1
  1. 1.Laboratory of Chemical PhysicsUniversity of GroningenGroningenThe Netherlands

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