Nobel Prizes for 3D Molecular Structure

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Nobel Prizes for X-Rays and Their Diffraction

  • 1914: Max von Laue (Physics) "for his discovery of the diffraction of X-rays by crystals".

Nobel Prizes for 3D Chemical Structure

  • 1915: Sir William Henry Bragg and William Lawrence Bragg (Physics) "for their services in the analysis of crystal structure by means of X-rays". Lawrence's Bragg Equation quantitatively explained the spots diffracted from a crystal, based on his understanding of crystal "lattice structure as being constructed from a series of sheets of atoms, laid one on top of another, with each sheet behaving like a mirror"[1]. Subsequently they solved the structures of crystals of NaCl, and of diamond, among others.
  • 1964: Dorothy Crowfoot Hodgkin (Chemistry) "for her determinations by X-ray techniques of the structures of important biochemical substances", including the structures of penicillin in 1949, and vitamin B-12 in 1957.
  • 2011: Dan Shechtman (Chemistry) "for the discovery of quasicrystals".

Nobel Prizes for 3D Macromolecular Structure and Structure Determination Methods

Twentieth Century

  • 1954: Linus Pauling (Chemistry) "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances", including prediction of the planarity of the peptide bond, and the structures of the alpha helix and beta strand in 1951[2].
  Image:Myoglobin1958.png
The first 3D protein structure: myoglobin at ~6 Å by Kendrew et al.. Adapted by permission from Macmillan Publishers Ltd: Nature 181:662, copyright 1958.Myoglobin (1mbn, 2.0 Å) deposited in the fledgling PDB in 1973 by Watson and Kendrew.
  • 1962: Max Ferdinand Perutz and John Cowdery Kendrew (Chemistry) "for their studies of the structures of globular proteins". With his coworkers, Kendrew obtained the first tertiary structure of a protein, myoglobin, in 1958 at about 6 Å resolution[3]. Subsequently, they published higher resolution solutions for myoglobin. This achievement depended on the discovery, by Perutz and coworkers five years earlier, of heavy metal isomorphous replacement for phase determination in X-ray diffraction. In 1960, Perutz and coworkers solved oxy-hemoglobin at 5.5 Å resolution[4]. The subsequent solution of deoxy hemoglobin by Muirhead and Perutz in 1962[5] revealed the first functionally crucial conformational change of a protein. Famously, in the 1958 paper on myoglobin[3], they concluded:
Perhaps the most remarkable features of the molecule are its complexity and its lack of symmetry. The arrangement seems to be almost totally lacking in the kind of regularities which one instinctively anticipates, and it is more complicated than has been predicated by any theory of protein structure.
  • 1962 Francis Harry Compton Crick, James Dewey Watson, and Maurice Hugh Frederick Wilkins (Physiology or Medicine) "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material". Although Watson and Crick's 1953 model[6] was theoretical, based in part on X-ray fiber diffraction, it was essentially correct, and for the first time explained the ability of genes to be faithfully copied during cell division. It was not confirmed by atomic resolution X-ray crystallography until 1973, using RNA dinucleotide crystals[7]. A full turn of B form DNA was not solved until 1980 (1BNA)[7], 27 years after Watson and Crick's model. X-ray diffraction data obtained by Rosalind E. Franklin (1920-1958) played an important role in Crick, Wilkins and Watson's model building, but she regrettably received inadequate credit in the 1953 publication[8].
  • 1972: Christian B. Anfinsen, Stanford Moore, and William H. Stein (Chemistry). Anfinsen "for his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation", and Moore and Stein "for their contribution to the understanding of the connection between chemical structure and catalytic activity of the active centre of the ribonuclease molecule". This prize was not for structure determination, but rather, in part, for determining the amino acids essential to the active site of the enzyme before the structure was determined. See also RNaseA Nobel Prizes. The structure of ribonuclease was reported independently by two groups in 1967[9]. It was the second enzyme structure to be solved, after lysozyme[9], and did not earn a Nobel prize.
  • 1982: Aaron Klug (Chemistry) "for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes". Klug and coworkers elucidated the structure of Tobacco Mosaic Virus and chromatin. The Nobel press release explains
His method allows electron microscope pictures of high quality to be obtained with very low radiation doses and without the use of heavy metal stains. In this way changes in the sample are minimized, so that the electron microscope picture at high resolution is a true representation of the original biological structure. The method gives a two-dimensional projection of the sample only, but Klug has shown that a three-dimensional reconstruction of the object can be obtained by collecting pictures in several different directions of projection.
  • 1991: Richard R. Ernst (Chemistry) "for his contributions to the development of the methodology of high resolution nuclear magnetic resonance (NMR) spectroscopy".
  • 1994: Bertram N. Brockhouse and Clifford G. Shull (Physics) "for pioneering contributions to the development of neutron scattering techniques for studies of condensed matter". From the Press Release: In simple terms, Clifford G. Shull has helped answer the question of where atoms "are" and Bertram N. Brockhouse the question of what atoms "do". Although neither name appears as a depositor on any entry in the PDB in 2008, there are 21 entries determined by neutron diffraction.
  • 1996: Paul D. Boyer, John E. Walker, and Jens C. Skou (Chemistry) "for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)". Walker's quarter of the prize was for the structure: see (from 1996) 1bmf, 1cow, and many subsequent structures.

Twenty-First Century

  • 2002: John B. Fenn, Koichi Tanaka, and Kurt Wüthrich (Chemistry) "for the development of methods for identification and structure analyses of biological macromolecules". Fenn and Tanaka each were awarded one quarter of the prize "for their development of soft desorption ionisation methods for mass spectrometric analyses of biological macromolecules", while Wüthrich received his half "for his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution".
  • 2003: Peter Agre and Roderick MacKinnon (Chemistry), Agre "for the discovery of water channels" and MacKinnon "for structural and mechanistic studies of ion channels". Structures by MacKinnon and his group began in 1998 with the transmembrane potassium channel 1bl8, and continued with many others. After this prize, Agre was involved in the structures reported in 2005, 2f2b and 2evu.
  • 2006: Roger Kornberg (Chemistry) "for his studies of the molecular basis of eukaryotic transcription". Kornberg and his group solved the structure of DNA-dependent RNA polymerase. In 1959, Roger saw his father Arthur Kornberg receive the Nobel Prize in Physiology or Medicine, with Severo Ochoa, for discovering DNA polymerase and describing the mechanism of DNA replication. The first RNA polymerase structures, from early 2001: 1i3q, 1i50, 1i6h, followed by others.

See Also

References

  1. Perspectives on the Nobel Prize in Physics for 1915, by Joachim Pietzsch.
  2. The Structure of Proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain, L. Pauling, R. B. Corey, and H. R. Branson, Proc. Natl. Acad. Sci. US 37:205, 1951.
  3. 3.0 3.1 A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. KENDREW JC, BODO G, DINTZIS HM, PARRISH RG, WYCKOFF H, PHILLIPS DC. Nature. 181:662-6, 1958. PubMed 13517261
  4. Structure of haemoglobin. A three-dimensional fourier syntheses at 5.5 Å resolution, obtained by X-ray analysis. M. F. Perutz, M. G. Rossman, A. F. Cullis, H. Muirhead, and G. Will. Nature 185:416, 1960. (Not in PubMed.)
  5. STRUCTURE OF HAEMOGLOBIN. A THREE-DIMENSIONAL FOURIER SYNTHESIS OF REDUCED HUMAN HAEMOGLOBIN AT 5-5 A RESOLUTION. MUIRHEAD H, PERUTZ MF. Nature. 199:633-8, 1963. PubMed 14074546
  6. Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid. J. D. WATSON, F. H. C. CRICK, Nature 171, 737 - 738, 1953. Free annotated PDF from the Exploratorium.
  7. 7.0 7.1 Nucleic acid crystallography: a view from the nucleic acid database. Berman HM, Gelbin A, Westbrook J. Prog Biophys Mol Biol. 66:255-88, 1996. PubMed 9284453
  8. Rosalind Franklin: Dark Lady of DNA by Brenda Maddox, HarperCollins, 2002
  9. 9.0 9.1 References and PDB codes will be found at Earliest Solutions for Macromolecular Crystal Structures.

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