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Protonation/Deprotonation of Proteins by Neutron Diffraction Structure Analysis

  • Ichiro Tanaka
  • Katsuhiro Kusaka
  • Nobuo Niimura
Chapter

Abstract

Neutron protein crystallography can reveal nuclear position and it is very useful to find hydrogen or protonation/deprotonation of protein. It is, however, an intensity-limited experiment and requires large and good quality single protein crystal, so the user population has been so small. Recently, new intense neutron source makes ones to find several protonation states in proteins; PcyA complex (complex of Phycocyanobilin: Ferredoxin Oxidoreductase and Biliverdin IXα), cellulase and substrate complex and farnesyl pyrophosphate synthase (FPPS)-drug complex. At the same time, new techniques for neutron measurement such as high pressure freezing and dynamic nuclear polarization of protein have been also tried to be developed. Finally, a plan of new neutron facility to gain more S/N ratio is expected so that the sample crystal volume can be much small to find protonation/deprotonation.

Keywords

Neutron protein crystallography Proton Dynamic nuclear polarization High-pressure freezing Spallation neutron source 

Notes

Acknowledgements

Authors would thank Profs. T. Iwata and Miyachi and their students in Yamagata University for conducting and discussing ESR and DNP measurements, Prof. Chatake in Kyoto University for preparation of protein crystals and discussion, Dr. T. Kumada in Japan Atomic Energy Agency (JAEA) for providing a radical concentration information, and Drs. H. Seto in High Energy Accelerator Research Organization (KEK) and Harada in JAEA for providing information of the second target station at MLF in J-PARC. Synchrotron radiation experiment was conducted at BL5A of the Photon Factory in KEK, Ibaraki, Japan [2014G650]. Finally, authors are profoundly grateful to iBIX users, Prof. T. Yamada, Dr. N. Yano, Mrs. S. Ninomiya and J. Hiroki, and all students in Tanaka laboratory in Ibaraki University.

References

  1. Adams PD, Afonine PV et al (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Cryst D66:213–221Google Scholar
  2. Arai S et al (2004) More rapid evaluation of biomacromolecular crystals for diffraction experiments. Acta Cryst D 60:1032–1039CrossRefGoogle Scholar
  3. Blakely M (2009) Neutron macromolecular crystallography. Cryst Rev 15:157–218CrossRefGoogle Scholar
  4. Bunyatova EI (1995) New investigations of organic compounds for targets with polarized hydrogen nuclei. Nucl Instrum Methods Phys Res A 356:29–33CrossRefGoogle Scholar
  5. Casadei CM et al (2014) Neutron cryo-crystallography captures the protonation state of ferryl heme in a peroxidase. Science 345:193–197CrossRefGoogle Scholar
  6. Coates L, Stoica AD, Hoffmann C, Richards J, Cooper R (2010) The macromolecular neutron diffractometer (MaNDi) at the Spallation Neutron Source, Oak Ridge: enhanced optics design, high-resolution neutron detectors and simulated diffraction. J Appl Cryst 43:570–577CrossRefGoogle Scholar
  7. de Boer W (1973) High proton polarization in 1,2-propanediol at 3He temperatures. Nucl Instrum Methods 107:99–104CrossRefGoogle Scholar
  8. Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Cryst D60:2126–2132Google Scholar
  9. Helliwell JR (1997) Neutron Laue diffraction does it faster. Nat Struct Mol Biol 4:874–876CrossRefGoogle Scholar
  10. Hosoya T et al (2009) Development of a new detector and DAQ systems for iBIX. Nucl Instrum Methods Phys Res A 600:217–219CrossRefGoogle Scholar
  11. J-PARC Center, MLF (2010) Report of J-PARC materials and life science experimental facility future planning task (in Japanese). J-PARC 10-02Google Scholar
  12. Kabsch W (2010) XDS. Acta Cryst D66:125–132Google Scholar
  13. Kim CU, Kapfer R, Gruner SM (2005) High-pressure cooling of protein crystals without cryoprotectants. Acta Cryst D61:881–890Google Scholar
  14. Kim CU et al (2016) Tracking solvent and protein movement during CO2 release in carbonic anhydrase II crystals. Proc Nat Acad Sci USA 113:5257–5262CrossRefGoogle Scholar
  15. Kumada T, Noda Y, Ishikawa N (2012) Dynamic nuclear polarization of electron-beam irradiated polyethylene by pairs of alkyl free radicals. J Magn Reson 218:59–65CrossRefGoogle Scholar
  16. Kurihara K, Tanaka I et al (2004) A new neutron single crystal diffractometer dedicated for biological macromolecules (BIX-4). J Synchrotron Radiat 11:68–71CrossRefGoogle Scholar
  17. Kusaka K et al (2013) Evaluation of performance for IBARAKI biological crystal diffractometer iBIX with new detectors. J Synchrotron Radiat 20:994–998CrossRefGoogle Scholar
  18. Meilleur F et al (2013) The IMAGINE instrument: first neutron protein structure and new capabilities for neutron macromolecular crystallography. Acta Cryst D 69:2157–2160CrossRefGoogle Scholar
  19. Mishima O (1996) Relationship between melting and amorphization of ice. Nature 384:546–549CrossRefGoogle Scholar
  20. Nakamura A et al (2015) “Newton’s cradle” proton relay with amide imidic acid tautomerization in inverting cellulase visualized by neutron crystallography. Sci Adv 1:e1500263 (2015)CrossRefGoogle Scholar
  21. Niimura N, Bau R (2008) Neutron protein crystallography: beyond the folding structure of biological macromolecules. Acta Cryst A64:12–22CrossRefGoogle Scholar
  22. Niimura N, Podjarny A (2011) Neutron protein crystallography: hydrogen, protons, and hydration in bio-macromolecules. In: IUCr monographs on crystallography 25. Oxford University Press, OxfordCrossRefGoogle Scholar
  23. Niimura N, Karasawa Y, Tanaka I et al (1994) An imaging plate neutron detector. Nucl Instrum Methods A349:521–525CrossRefGoogle Scholar
  24. Niimura N, Minezaki Y et al (1997) Neutron Laue diffractometry with an imaging plate provides an effective data collection regime for neutron protein crystallography. Nat Struct Mol Biol 4:909–914CrossRefGoogle Scholar
  25. Niimura N, Takimoto-Kamimura M, Tanaka I (2016) Application of neutron diffraction in studies of protein dynamics and functions. In: Encyclopedia of analytical chemistry. Wiley, New York, pp 1–30Google Scholar
  26. NMX (Macromolecular Diffractometer) at ESS (European Spallation Source) (2017). https://europeanspallationsource.se/instruments/nmx. Accessed 20 Nov 2017
  27. Ohhara T et al (2009) Development of data processing software for a new TOF single crystal neutron diffractometer at J-PARC. Nucl Instrum Methods A 600:195–197CrossRefGoogle Scholar
  28. Ostermann A, Schrader T (2015) BIODIFF: diffractometer for large unit cells. J Large-Scale Res Facil 1:A2CrossRefGoogle Scholar
  29. Otwinowski Z, Minor W (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276:307–326CrossRefGoogle Scholar
  30. Piegsa FM et al (2013) Polarized neutron Laue diffraction on a crystal containing dynamically polarized proton spins. J Appl Cryst 46:30–34CrossRefGoogle Scholar
  31. Stuhrmann HB (2004) Unique aspects of neutron scattering for the study of biological systems. Rep Prog Phys 67:1073–1115CrossRefGoogle Scholar
  32. Tanaka I et al (2002) A high-performance neutron diffractometer for biological crystallography (BIX-3). J Appl Cryst 35:34–40CrossRefGoogle Scholar
  33. Tanaka I et al (2010) Neutron structure analysis by IBARAKI biological crystal diffractometer (iBIX) in J-PARC. Acta Cryst D66:1194–1197Google Scholar
  34. Tanaka I, Komatsuzaki N et al (2018) Cryoprotectant-free high-pressure freezing and dynamic nuclear polarization for more sensitive detection of hydrogen in neutron protein crystallography. Acta Cryst D. (submitted)Google Scholar
  35. Tanaka I, Kusaka K et al (2009) Overview of a new biological neutron diffractometer (iBIX) in J-PARC. Nucl Instrum Methods A 600:161–163CrossRefGoogle Scholar
  36. Tanaka I, Kusaka K, Chatake T, Niimura N (2013) Fundamental studies for the proton polarization technique in neutron protein crystallography. J Synchrotron Radiat 20:958–961CrossRefGoogle Scholar
  37. Unno M et al (2015) Insights into the proton transfer mechanism of a bilin reductase PcyA following neutron crystallography. J Am Chem Soc 137:5452–5460CrossRefGoogle Scholar
  38. Yano N et al (2016) Application of profile fitting method to neutron time-of-flight protein single crystal diffraction data collected at the iBIX. Sci Rep 6:36628CrossRefGoogle Scholar
  39. Yokoyama T et al (2015) Protonation state and hydration of bisphosphonate bound to farnesyl pyrophosphate synthase. J Med Chem 58:7549–7556CrossRefGoogle Scholar
  40. Zhao JK, Robertson L, Herwig K, Crabb D (2013) Polarized neutron in structural biology—present and future outlook. Phys Procedia 42:39–45CrossRefGoogle Scholar
  41. Zimmer O, Jouve HM, Stuhrmann HB (2016) Polarized proton spin density images the tyrosyl radical locations in bovine liver catalase. IUCr J 3:326–340CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Ichiro Tanaka
    • 1
  • Katsuhiro Kusaka
    • 2
  • Nobuo Niimura
    • 2
  1. 1.College of EngineeringIbaraki UniversityHitachiJapan
  2. 2.Frontier Research Center for Applied Atomic SciencesIbaraki UniversityTokaiJapan

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