1932

Abstract

Directly observing enzyme catalysis in real time at the molecular level has been a long-standing goal of structural enzymology. Time-resolved serial crystallography methods at synchrotron and X-ray free electron laser (XFEL) sources have enabled researchers to follow enzyme catalysis and other nonequilibrium events at ambient conditions with unprecedented time resolution. X-ray crystallography provides detailed information about conformational heterogeneity and protein dynamics, which is enhanced when time-resolved approaches are used. This review outlines the ways in which information about the underlying energy landscape of a protein can be extracted from X-ray crystallographic data, with an emphasis on new developments in XFEL and synchrotron time-resolved crystallography. The emerging view of enzyme catalysis afforded by these techniques can be interpreted as enzymes moving on a time-dependent energy landscape. Some consequences of this view are discussed, including the proposal that irreversible enzymes or enzymes that use covalent catalytic mechanisms may commonly exhibit catalysis-activated motions.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-100421-110959
2022-05-09
2024-05-14
Loading full text...

Full text loading...

/deliver/fulltext/biophys/51/1/annurev-biophys-100421-110959.html?itemId=/content/journals/10.1146/annurev-biophys-100421-110959&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Alber T, Petsko GA, Tsernoglou D. 1976. Crystal structure of elastase-substrate complex at –55 degrees C. Nature 263:297–300
    [Google Scholar]
  2. 2.
    Ansari A, Berendzen J, Bowne SF, Frauenfelder H, Iben IE et al. 1985. Protein states and proteinquakes. PNAS 82:5000–4
    [Google Scholar]
  3. 3.
    Arora K, Brooks CL 3rd 2007. Large-scale allosteric conformational transitions of adenylate kinase appear to involve a population-shift mechanism. PNAS 104:18496–501
    [Google Scholar]
  4. 4.
    Barends TR, Foucar L, Ardevol A, Nass K, Aquila A et al. 2015. Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation. Science 350:445–50
    [Google Scholar]
  5. 5.
    Barty A, Caleman C, Aquila A, Timneanu N, Lomb L et al. 2012. Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements. Nat. Photon. 6:35–40
    [Google Scholar]
  6. 6.
    Benkovic SJ, Hammes GG, Hammes-Schiffer S. 2008. Free-energy landscape of enzyme catalysis. Biochemistry 47:3317–21
    [Google Scholar]
  7. 7.
    Boutet S, Lomb L, Williams GJ, Barends TR, Aquila A et al. 2012. High-resolution protein structure determination by serial femtosecond crystallography. Science 337:362–64
    [Google Scholar]
  8. 8.
    Bryngelson JD, Onuchic JN, Socci ND, Wolynes PG. 1995. Funnels, pathways, and the energy landscape of protein folding: a synthesis. Proteins 21:167–95
    [Google Scholar]
  9. 9.
    Budday D, Leyendecker S, van den Bedem H. 2018. Kinematic flexibility analysis: Hydrogen bonding patterns impart a spatial hierarchy of protein motion. J. Chem. Inf. Model. 58:2108–22
    [Google Scholar]
  10. 10.
    Burling FT, Brunger AT. 1994. Thermal motion and conformational disorder in protein crystal structures: comparison of multi-conformer and time-averaging models. Israel J. Chem. 34:165–72
    [Google Scholar]
  11. 11.
    Burling FT, Weis WI, Flaherty KM, Brunger AT. 1996. Direct observation of protein solvation and discrete disorder with experimental crystallographic phases. Science 271:72–77
    [Google Scholar]
  12. 12.
    Burnley BT, Afonine PV, Adams PD, Gros P 2012. Modelling dynamics in protein crystal structures by ensemble refinement. eLife 1:e00311
    [Google Scholar]
  13. 13.
    Callen HB, Welton TA. 1951. Irreversibility and generalized noise. Phys. Rev. 83:34–40
    [Google Scholar]
  14. 14.
    Calvey GD, Katz AM, Schaffer CB, Pollack L. 2016. Mixing injector enables time-resolved crystallography with high hit rate at X-ray free electron lasers. Struct. Dyn. 3:054301
    [Google Scholar]
  15. 15.
    Chapman HN. 2017. Structure determination using X-ray free-electron laser pulses. Methods Mol. Biol. 1607:295–324
    [Google Scholar]
  16. 16.
    Chapman HN, Barty A, Bogan MJ, Boutet S, Frank M et al. 2006. Femtosecond diffractive imaging with a soft-X-ray free-electron laser. Nat. Phys. 2:839–43
    [Google Scholar]
  17. 17.
    Chapman HN, Caleman C, Timneanu N. 2014. Diffraction before destruction. Philos. Trans. R. Soc. B 369:20130313
    [Google Scholar]
  18. 18.
    Chapman HN, Fromme P, Barty A, White TA, Kirian RA et al. 2011. Femtosecond X-ray protein nanocrystallography. Nature 470:73–77
    [Google Scholar]
  19. 19.
    Chen X, Poon BK, Dousis A, Wang Q, Ma J 2007. Normal-mode refinement of anisotropic thermal parameters for potassium channel KcsA at 3.2 Å crystallographic resolution. Structure 15:955–62
    [Google Scholar]
  20. 20.
    Cheng RKY. 2020. Towards an optimal sample delivery method for serial crystallography at XFEL. Crystals 10:215
    [Google Scholar]
  21. 21.
    Church BW, Shalloway D. 2001. Top-down free-energy minimization on protein potential energy landscapes. PNAS 98:6098–103
    [Google Scholar]
  22. 22.
    Clarage JB, Clarage MS, Phillips WC, Sweet RM, Caspar DL. 1992. Correlations of atomic movements in lysozyme crystals. Proteins 12:145–57
    [Google Scholar]
  23. 23.
    Clinger JA, Moreau DW, McLeod MJ, Holyoak T, Thorne RE. 2021. Millisecond mix-and-quench crystallography (MMQX) enables time-resolved studies of PEPCK with remote data collection. IUCrJ 8:784–92
    [Google Scholar]
  24. 24.
    Coquelle N, Sliwa M, Woodhouse J, Schiro G, Adam V et al. 2018. Chromophore twisting in the excited state of a photoswitchable fluorescent protein captured by time-resolved serial femtosecond crystallography. Nat. Chem. 10:31–37
    [Google Scholar]
  25. 25.
    Dasgupta M, Budday D, de Oliveira SHP, Madzelan P, Marchany-Rivera D et al. 2019. Mix-and-inject XFEL crystallography reveals gated conformational dynamics during enzyme catalysis. PNAS 116:25634–40
    [Google Scholar]
  26. 26.
    Denes P. 2014. Two-dimensional imaging detectors for structural biology with X-ray lasers. Philos. Trans. R. Soc. Lond. B 369:20130334
    [Google Scholar]
  27. 27.
    DePonte DP, Weierstall U, Schmidt K, Warner J, Starodub D et al. 2008. Gas dynamic virtual nozzle for generation of microscopic droplet streams. J. Phys. D 41:19
    [Google Scholar]
  28. 28.
    Diamond R. 1990. On the use of normal modes in thermal parameter refinement: theory and application to the bovine pancreatic trypsin inhibitor. Acta Crystallogr. A 46:Pt. 6425–35
    [Google Scholar]
  29. 29.
    Dill KA, Chan HS. 1997. From Levinthal to pathways to funnels. Nat. Struct. Biol. 4:10–19
    [Google Scholar]
  30. 30.
    Eisenmesser EZ, Bosco DA, Akke M, Kern D. 2002. Enzyme dynamics during catalysis. Science 295:1520–23
    [Google Scholar]
  31. 31.
    Farber GK, Glasfeld A, Tiraby G, Ringe D, Petsko GA 1989. Crystallographic studies of the mechanism of xylose isomerase. Biochemistry 28:7289–97
    [Google Scholar]
  32. 32.
    Fenwick RB, van den Bedem H, Fraser JS, Wright PE 2014. Integrated description of protein dynamics from room-temperature X-ray crystallography and NMR. PNAS 111:E445–54
    [Google Scholar]
  33. 33.
    Fraser JS, Clarkson MW, Degnan SC, Erion R, Kern D, Alber T. 2009. Hidden alternative structures of proline isomerase essential for catalysis. Nature 462:669–73
    [Google Scholar]
  34. 34.
    Fraser JS, van den Bedem H, Samelson AJ, Lang PT, Holton JM et al. 2011. Accessing protein conformational ensembles using room-temperature X-ray crystallography. PNAS 108:16247–52
    [Google Scholar]
  35. 35.
    Frauenfelder H, Sligar SG, Wolynes PG. 1991. The energy landscapes and motions of proteins. Science 254:1598–603
    [Google Scholar]
  36. 36.
    Frederick KK, Marlow MS, Valentine KG, Wand AJ. 2007. Conformational entropy in molecular recognition by proteins. Nature 448:325–29
    [Google Scholar]
  37. 37.
    Fuller FD, Gul S, Chatterjee R, Burgie ES, Young ID et al. 2017. Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers. Nat. Methods 14:443–49
    [Google Scholar]
  38. 38.
    Genick UK, Borgstahl GE, Ng K, Ren Z, Pradervand C et al. 1997. Structure of a protein photocycle intermediate by millisecond time-resolved crystallography. Science 275:1471–75
    [Google Scholar]
  39. 39.
    Genick UK, Soltis SM, Kuhn P, Canestrelli IL, Getzoff ED. 1998. Structure at 0.85 Å resolution of an early protein photocycle intermediate. Nature 392:206–9
    [Google Scholar]
  40. 40.
    Gros P, van Gunsteren WF, Hol WG. 1990. Inclusion of thermal motion in crystallographic structures by restrained molecular dynamics. Science 249:1149–52
    [Google Scholar]
  41. 41.
    Grunbein ML, Bielecki J, Gorel A, Stricker M, Bean R et al. 2018. Megahertz data collection from protein microcrystals at an X-ray free-electron laser. Nat. Commun. 9:3487
    [Google Scholar]
  42. 42.
    Grunbein ML, Stricker M, Nass Kovacs G, Kloos M, Doak RB et al. 2020. Illumination guidelines for ultrafast pump-probe experiments by serial femtosecond crystallography. Nat. Methods 17:681–84
    [Google Scholar]
  43. 43.
    Hajdu J, Acharya KR, Stuart DI, McLaughlin PJ, Barford D et al. 1987. Catalysis in the crystal: synchrotron radiation studies with glycogen phosphorylase b. EMBO J 6:539–46
    [Google Scholar]
  44. 44.
    Halle B. 2004. Biomolecular cryocrystallography: structural changes during flash-cooling. PNAS 101:4793–98
    [Google Scholar]
  45. 45.
    Hatsui T, Graafsma H. 2015. X-ray imaging detectors for synchrotron and XFEL sources. IUCrJ 2:371–83
    [Google Scholar]
  46. 46.
    Hirata K, Shinzawa-Itoh K, Yano N, Takemura S, Kato K et al. 2014. Determination of damage-free crystal structure of an X-ray-sensitive protein using an XFEL. Nat. Methods 11:734–36
    [Google Scholar]
  47. 47.
    Hu X, Hong L, Smith MD, Neusius T, Cheng X, Smith JC. 2015. The dynamics of single protein molecules is non-equilibrium and self-similar over thirteen decades in time. Nat. Phys. 12:171–74
    [Google Scholar]
  48. 48.
    Hunter MS, Segelke B, Messerschmidt M, Williams GJ, Zatsepin NA et al. 2014. Fixed-target protein serial microcrystallography with an X-ray free electron laser. Sci. Rep. 4:6026
    [Google Scholar]
  49. 49.
    Ihee H, Rajagopal S, Srajer V, Pahl R, Anderson S et al. 2005. Visualizing reaction pathways in photoactive yellow protein from nanoseconds to seconds. PNAS 102:7145–50
    [Google Scholar]
  50. 50.
    Ishigami I, Lewis-Ballester A, Echelmeier A, Brehm G, Zatsepin NA et al. 2019. Snapshot of an oxygen intermediate in the catalytic reaction of cytochrome c oxidase. PNAS 116:3572–77
    [Google Scholar]
  51. 51.
    Ishigami I, Zatsepin NA, Hikita M, Conrad CE, Nelson G et al. 2017. Crystal structure of CO-bound cytochrome c oxidase determined by serial femtosecond X-ray crystallography at room temperature. PNAS 114:8011–16
    [Google Scholar]
  52. 52.
    Jee AY, Cho YK, Granick S, Tlusty T. 2018. Catalytic enzymes are active matter. PNAS 115:E10812–21
    [Google Scholar]
  53. 53.
    Jones HBL, Wells SA, Prentice EJ, Kwok A, Liang LL et al. 2017. A complete thermodynamic analysis of enzyme turnover links the free energy landscape to enzyme catalysis. FEBS J 284:2829–42
    [Google Scholar]
  54. 54.
    Kamerlin SC, Warshel A. 2010. At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?. Proteins 78:1339–75
    [Google Scholar]
  55. 55.
    Karplus M. 2011. Behind the folding funnel diagram. Nat. Chem. Biol. 7:401–4
    [Google Scholar]
  56. 56.
    Keedy DA, Fraser JS, van den Bedem H. 2015. Exposing hidden alternative backbone conformations in X-ray crystallography using qFit. PLOS Comput. Biol. 11:e1004507
    [Google Scholar]
  57. 57.
    Keedy DA, Kenner LR, Warkentin M, Woldeyes RA, Hopkins JB et al. 2015. Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography. eLife 4:e07574
    [Google Scholar]
  58. 58.
    Keedy DA, van den Bedem H, Sivak DA, Petsko GA, Ringe D et al. 2014. Crystal cryocooling distorts conformational heterogeneity in a model Michaelis complex of DHFR. Structure 22:899–910
    [Google Scholar]
  59. 59.
    Kern J, Chatterjee R, Young ID, Fuller FD, Lassalle L et al. 2018. Structures of the intermediates of Kok's photosynthetic water oxidation clock. Nature 563:421–25
    [Google Scholar]
  60. 60.
    Key J, Srajer V, Pahl R, Moffat K 2007. Time-resolved crystallographic studies of the heme domain of the oxygen sensor FixL: structural dynamics of ligand rebinding and their relation to signal transduction. Biochemistry 46:4706–15
    [Google Scholar]
  61. 61.
    Kidera A, Inaka K, Matsushima M, Go N 1992. Normal mode refinement: crystallographic refinement of protein dynamic structure. II. Application to human lysozyme. J. Mol. Biol. 225:477–86
    [Google Scholar]
  62. 62.
    Kim TH, Mehrabi P, Ren Z, Sljoka A, Ing C et al. 2017. The role of dimer asymmetry and protomer dynamics in enzyme catalysis. Science 355:eaag2355
    [Google Scholar]
  63. 63.
    Kohen A. 2015. Role of dynamics in enzyme catalysis: substantial versus semantic controversies. ACC Chem. Res. 48:466–73
    [Google Scholar]
  64. 64.
    Kostov KS, Moffat K. 2011. Cluster analysis of time-dependent crystallographic data: direct identification of time-independent structural intermediates. Biophys. J. 100:440–49
    [Google Scholar]
  65. 65.
    Kupitz C, Basu S, Grotjohann I, Fromme R, Zatsepin NA et al. 2014. Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser. Nature 513:261–65
    [Google Scholar]
  66. 66.
    Kupitz C, Olmos JL Jr., Holl M, Tremblay L, Pande K et al. 2017. Structural enzymology using X-ray free electron lasers. Struct. Dyn. 4:044003
    [Google Scholar]
  67. 67.
    Kuzmanic A, Pannu NS, Zagrovic B. 2014. X-ray refinement significantly underestimates the level of microscopic heterogeneity in biomolecular crystals. Nat. Commun. 5:3220
    [Google Scholar]
  68. 68.
    Kwon H, Basran J, Pathak C, Hussain M, Freeman SL et al. 2021. XFEL crystal structures of peroxidase compound II. Angew. Chem. Int. Ed. Engl. 60:14578–85
    [Google Scholar]
  69. 69.
    Lakshminarasimhan M, Madzelan P, Nan R, Milkovic NM, Wilson MA 2010. Evolution of new enzymatic function by structural modulation of cysteine reactivity in Pseudomonas fluorescens isocyanide hydratase. J. Biol. Chem. 285:29651–61
    [Google Scholar]
  70. 70.
    Lehwess-Litzmann A, Neumann P, Parthier C, Ludtke S, Golbik R et al. 2011. Twisted Schiff base intermediates and substrate locale revise transaldolase mechanism. Nat. Chem. Biol. 7:678–84
    [Google Scholar]
  71. 71.
    Levin EJ, Kondrashov DA, Wesenberg GE, Phillips GN Jr 2007. Ensemble refinement of protein crystal structures: validation and application. Structure 15:1040–52
    [Google Scholar]
  72. 72.
    Lu W, Friedrich B, Noll T, Zhou K, Hallmann J et al. 2018. Development of a hard X-ray split-and-delay line and performance simulations for two-color pump-probe experiments at the European XFEL. Rev. Sci. Instrum. 89:063121
    [Google Scholar]
  73. 73.
    Matyushov DV. 2018. Fluctuation relations, effective temperature, and ageing of enzymes: the case of protein electron transfer. J. Mol. Liquids 266:361–72
    [Google Scholar]
  74. 74.
    Meents A, Wiedorn MO, Srajer V, Henning R, Sarrou I et al. 2017. Pink-beam serial crystallography. Nat. Commun. 8:1281
    [Google Scholar]
  75. 75.
    Mehrabi P, Bucker R, Bourenkov G, Ginn HM, von Stetten D et al. 2021. Serial femtosecond and serial synchrotron crystallography can yield data of equivalent quality: a systematic comparison. Sci. Adv 7:eabf1380
    [Google Scholar]
  76. 76.
    Mehrabi P, Schulz EC, Dsouza R, Muller-Werkmeister HM, Tellkamp F et al. 2019. Time-resolved crystallography reveals allosteric communication aligned with molecular breathing. Science 365:1167–70
    [Google Scholar]
  77. 77.
    Meisburger SP, Case DA, Ando N 2020. Diffuse X-ray scattering from correlated motions in a protein crystal. Nat. Commun. 11:1271
    [Google Scholar]
  78. 78.
    Moffat K. 1989. Time-resolved macromolecular crystallography. Annu. Rev. Biophys. Biophys. Chem. 18:309–32
    [Google Scholar]
  79. 79.
    Nango E, Royant A, Kubo M, Nakane T, Wickstrand C et al. 2016. A three-dimensional movie of structural changes in bacteriorhodopsin. Science 354:1552–57
    [Google Scholar]
  80. 80.
    Neutze R. 2014. Opportunities and challenges for time-resolved studies of protein structural dynamics at X-ray free-electron lasers. Philos. Trans. R. Soc. Lond. B 369:20130318
    [Google Scholar]
  81. 81.
    Neutze R, Wouts R, van der Spoel D, Weckert E, Hajdu J 2000. Potential for biomolecular imaging with femtosecond X-ray pulses. Nature 406:752–57
    [Google Scholar]
  82. 82.
    Noe F, Schutte C, Vanden-Eijnden E, Reich L, Weikl TR. 2009. Constructing the equilibrium ensemble of folding pathways from short off-equilibrium simulations. PNAS 106:19011–16
    [Google Scholar]
  83. 83.
    Olmos JL Jr., Pandey S, Martin-Garcia JM, Calvey G, Katz A et al. 2018. Enzyme intermediates captured “on the fly” by mix-and-inject serial crystallography. BMC Biol 16:59
    [Google Scholar]
  84. 84.
    Orville AM. 2020. Recent results in time resolved serial femtosecond crystallography at XFELs. Curr. Opin. Struct. Biol. 65:193–208
    [Google Scholar]
  85. 85.
    Pandey S, Bean R, Sato T, Poudyal I, Bielecki J et al. 2020. Time-resolved serial femtosecond crystallography at the European XFEL. Nat. Methods 17:73–78
    [Google Scholar]
  86. 86.
    Pandey S, Calvey G, Katz AM, Malla TN, Koua FHM et al. 2021. Direct observation of the mechanism of antibiotic resistance by mix-and-inject at the European XFEL. bioRxiv 2020.11.24.396689. https://doi.org/10.1101/2020.11.24.396689
    [Crossref]
  87. 87.
    Pearson AR, Mehrabi P. 2020. Serial synchrotron crystallography for time-resolved structural biology. Curr. Opin. Struct. Biol. 65:168–74
    [Google Scholar]
  88. 88.
    Petsko GA. 1992. Art is long and time is fleeting: the current problems and future prospects for time-resolved enzyme crystallography. Philos. Trans. R. Soc. A 340:323–34
    [Google Scholar]
  89. 89.
    Rose SL, Antonyuk SV, Sasaki D, Yamashita K, Hirata K et al. 2021. An unprecedented insight into the catalytic mechanism of copper nitrite reductase from atomic-resolution and damage-free structures. Sci. Adv 7:abd8523
    [Google Scholar]
  90. 90.
    Schlichting I, Almo SC, Rapp G, Wilson K, Petratos K et al. 1990. Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis. Nature 345:309–15
    [Google Scholar]
  91. 91.
    Schlichting I, Berendzen J, Chu K, Stock AM, Maves SA et al. 2000. The catalytic pathway of cytochrome p450cam at atomic resolution. Science 287:1615–22
    [Google Scholar]
  92. 92.
    Schmidt M. 2013. Mix and inject: reaction initiation by diffusion for time-resolved macromolecular crystallography. Adv. Condensed Matter. Phys. 2013.167276
    [Google Scholar]
  93. 93.
    Schmidt M, Rajagopal S, Ren Z, Moffat K 2003. Application of singular value decomposition to the analysis of time-resolved macromolecular X-ray data. Biophys. J. 84:2112–29
    [Google Scholar]
  94. 94.
    Schomaker V, Trueblood KN. 1968. On the rigid-body motion of molecules in crystals. Acta Crystallogr. B 24:63–76
    [Google Scholar]
  95. 95.
    Schotte F, Lim M, Jackson TA, Smirnov AV, Soman J et al. 2003. Watching a protein as it functions with 150-ps time-resolved X-ray crystallography. Science 300:1944–47
    [Google Scholar]
  96. 96.
    Shimada A, Kubo M, Baba S, Yamashita K, Hirata K et al. 2017. A nanosecond time-resolved XFEL analysis of structural changes associated with CO release from cytochrome c oxidase. Sci. Adv. 3:e1603042
    [Google Scholar]
  97. 97.
    Sierra RG, Gati C, Laksmono H, Dao EH, Gul S et al. 2016. Concentric-flow electrokinetic injector enables serial crystallography of ribosome and photosystem II. Nat. Methods 13:59–62
    [Google Scholar]
  98. 98.
    Smith JL, Hendrickson WA, Honzatko RB, Sheriff S. 1986. Structural heterogeneity in protein crystals. Biochemistry 25:5018–27
    [Google Scholar]
  99. 99.
    Sorigue D, Hadjidemetriou K, Blangy S, Gotthard G, Bonvalet A et al. 2021. Mechanism and dynamics of fatty acid photodecarboxylase. Science 372:eabd5687
    [Google Scholar]
  100. 100.
    Spence JCH. 2017. XFELs for structure and dynamics in biology. IUCrJ 4:322–39
    [Google Scholar]
  101. 101.
    Srajer V, Teng T, Ursby T, Pradervand C, Ren Z et al. 1996. Photolysis of the carbon monoxide complex of myoglobin: nanosecond time-resolved crystallography. Science 274:1726–29
    [Google Scholar]
  102. 102.
    Srinivas V, Banerjee R, Lebrette H, Jones JC, Aurelius O et al. 2020. High-resolution XFEL structure of the soluble methane monooxygenase hydroxylase complex with its regulatory component at ambient temperature in two oxidation states. J. Am. Chem. Soc. 142:14249–66
    [Google Scholar]
  103. 103.
    Stagno JR, Liu Y, Bhandari YR, Conrad CE, Panja S et al. 2017. Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography. Nature 541:242–46
    [Google Scholar]
  104. 104.
    Stoddard BL, Cohen BE, Brubaker M, Mesecar AD, Koshland DE Jr 1998. Millisecond Laue structures of an enzyme-product complex using photocaged substrate analogs. Nat. Struct. Biol. 5:891–97
    [Google Scholar]
  105. 105.
    Stoddard BL, Koenigs P, Porter N, Petratos K, Petsko GA, Ringe D. 1991. Observation of the light-triggered binding of pyrone to chymotrypsin by Laue X-ray crystallography. PNAS 88:5503–7
    [Google Scholar]
  106. 106.
    Suga M, Akita F, Sugahara M, Kubo M, Nakajima Y et al. 2017. Light-induced structural changes and the site of O=O bond formation in PSII caught by XFEL. Nature 543:131–35
    [Google Scholar]
  107. 107.
    Teeter MM, Roe SM, Heo NH. 1993. Atomic resolution (0.83 Å) crystal structure of the hydrophobic protein crambin at 130 K. J. Mol. Biol. 230:292–311
    [Google Scholar]
  108. 108.
    Tenboer J, Basu S, Zatsepin N, Pande K, Milathianaki D et al. 2014. Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein. Science 346:1242–46
    [Google Scholar]
  109. 109.
    Tosha T, Nomura T, Nishida T, Saeki N, Okubayashi K et al. 2017. Capturing an initial intermediate during the P450nor enzymatic reaction using time-resolved XFEL crystallography and caged-substrate. Nat. Commun. 8:1585
    [Google Scholar]
  110. 110.
    Trueblood KN, Burgi H-B, Burzlaff H, Dunitz JD, Gramaccioli CM et al. 1996. Atomic displacement parameter nomenclature: report of a subcommittee on atomic displacement parameter nomenclature. Acta Crystallogr. A 52:770–81
    [Google Scholar]
  111. 111.
    van den Bedem H, Bhabha G, Yang K, Wright PE, Fraser JS 2013. Automated identification of functional dynamic contact networks from X-ray crystallography. Nat. Methods 10:896–902
    [Google Scholar]
  112. 112.
    van den Bedem H, Dhanik A, Latombe JC, Deacon AM. 2009. Modeling discrete heterogeneity in X-ray diffraction data by fitting multi-conformers. Acta Crystallogr. D 65:1107–17
    [Google Scholar]
  113. 113.
    Wales DJ, Bogdan TV. 2006. Potential energy and free energy landscapes. J. Phys. Chem. B 110:20765–76
    [Google Scholar]
  114. 114.
    Wall ME, Clarage JB, Phillips GN. 1997. Motions of calmodulin characterized using both Bragg and diffuse X-ray scattering. Structure 5:1599–612
    [Google Scholar]
  115. 115.
    Wall ME, Ealick SE, Gruner SM. 1997. Three-dimensional diffuse X-ray scattering from crystals of Staphylococcal nuclease. PNAS 94:6180–84
    [Google Scholar]
  116. 116.
    Wall ME, Van Benschoten AH, Sauter NK, Adams PD, Fraser JS, Terwilliger TC 2014. Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering. PNAS 111:17887–92
    [Google Scholar]
  117. 117.
    Wand AJ, Sharp KA. 2018. Measuring entropy in molecular recognition by proteins. Annu. Rev. Biophys. 47:41–61
    [Google Scholar]
  118. 118.
    Wang D, Weierstall U, Pollack L, Spence J. 2014. Double-focusing mixing jet for XFEL study of chemical kinetics. J. Synchrotron Radiat. 21:1364–66
    [Google Scholar]
  119. 119.
    Wang J. 2015. Landscape and flux theory of non-equilibrium dynamical systems with application to biology. Adv. Phys. 64:1–137
    [Google Scholar]
  120. 120.
    Warshel A, Bora RP. 2016. Perspective: defining and quantifying the role of dynamics in enzyme catalysis. J. Chem. Phys. 144:180901
    [Google Scholar]
  121. 121.
    Weber JK, Shukla D, Pande VS. 2015. Heat dissipation guides activation in signaling proteins. PNAS 112:10377–82
    [Google Scholar]
  122. 122.
    Weierstall U, James D, Wang C, White TA, Wang D et al. 2014. Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat. Commun. 5:3309
    [Google Scholar]
  123. 123.
    Wickstrand C, Katona G, Nakane T, Nogly P, Standfuss J et al. 2020. A tool for visualizing protein motions in time-resolved crystallography. Struct. Dyn. 7:024701
    [Google Scholar]
  124. 124.
    Willis BTM, Pryor AW. 1975. Thermal Vibrations in Crystallography Cambridge, UK: Cambridge Univ. Press
  125. 125.
    Wilson MA, Brunger AT. 2000. The 1.0 Å crystal structure of Ca2+-bound calmodulin: an analysis of disorder and implications for functionally relevant plasticity. J. Mol. Biol. 301:1237–56
    [Google Scholar]
  126. 126.
    Winn MD, Isupov MN, Murshudov GN. 2001. Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallogr. D 57:122–33
    [Google Scholar]
  127. 127.
    Wrabl JO, Gu J, Liu T, Schrank TP, Whitten ST, Hilser VJ. 2011. The role of protein conformational fluctuations in allostery, function, and evolution. Biophys. Chem. 159:129–41
    [Google Scholar]
  128. 128.
    Yabukarski F, Biel JT, Pinney MM, Doukov T, Powers AS et al. 2020. Assessment of enzyme active site positioning and tests of catalytic mechanisms through X-ray-derived conformational ensembles. PNAS 117:33204–15
    [Google Scholar]
  129. 129.
    Young ID, Ibrahim M, Chatterjee R, Gul S, Fuller F et al. 2016. Structure of photosystem II and substrate binding at room temperature. Nature 540:453–57
    [Google Scholar]
/content/journals/10.1146/annurev-biophys-100421-110959
Loading
/content/journals/10.1146/annurev-biophys-100421-110959
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error