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1. Megahertz pulse trains enable multi-hit serial femtosecond crystallography experiments at X-ray free electron lasers

Author

Holmes, Susannah, Kirkwood, Henry J, Bean, Richard, Giewekemeyer, Klaus, Martin, Andrew V, Hadian-Jazi, Marjan, Wiedorn, Max O, Oberthür, Dominik, Marman, Hugh, Adriano, Luigi, Al-Qudami, Nasser, Bajt, Saša, Barák, Imrich, Bari, Sadia, Bielecki, Johan, Brockhauser, Sandor, Coleman, Mathew A, Cruz-Mazo, Francisco, Danilevski, Cyril, Dörner, Katerina, Gañán-Calvo, Alfonso M, Graceffa, Rita, Fanghor, Hans, Heymann, Michael, Frank, Matthias, Kaukher, Alexander, Kim, Yoonhee, Kobe, Bostjan, Knoška, Juraj, Laurus, Torsten, Letrun, Romain, Maia, Luis, Messerschmidt, Marc, Metz, Markus, Michelat, Thomas, Mills, Grant, Molodtsov, Serguei, Monteiro, Diana CF, Morgan, Andrew J, Münnich, Astrid, Peña Murillo, Gisel E, Previtali, Gianpietro, Round, Adam, Sato, Tokushi, Schubert, Robin, Schulz, Joachim, Shelby, Megan, Seuring, Carolin, Sellberg, Jonas A, Sikorski, Marcin, Silenzi, Alessandro, Stern, Stephan, Sztuk-Dambietz, Jola, Szuba, Janusz, Trebbin, Martin, Vagovic, Patrick, Ve, Thomas, Weinhausen, Britta, Wrona, Krzysztof, Xavier, Paul Lourdu, Xu, Chen, Yefanov, Oleksandr, Nugent, Keith A, Chapman, Henry N, Mancuso, Adrian P, Barty, Anton, Abbey, Brian, and Darmanin, Connie

Subjects
Inorganic Chemistry, Chemical Sciences, Physical Sciences, Biological Sciences, Crystallography, X-Ray, Electrons, Lasers, Radiography, X-Rays
Abstract

The European X-ray Free Electron Laser (XFEL) and Linac Coherent Light Source (LCLS) II are extremely intense sources of X-rays capable of generating Serial Femtosecond Crystallography (SFX) data at megahertz (MHz) repetition rates. Previous work has shown that it is possible to use consecutive X-ray pulses to collect diffraction patterns from individual crystals. Here, we exploit the MHz pulse structure of the European XFEL to obtain two complete datasets from the same lysozyme crystal, first hit and the second hit, before it exits the beam. The two datasets, separated by

Published
2022

2. Identification of Selective Imidazopyridine CSF1R Inhibitors

Author

Kane, John L., primary, Asmussen, Gary, additional, Batchelor, Joseph, additional, Cromwell, Mandy, additional, Fezoui, Malika, additional, Fitzgerald, Maria, additional, Giese, Barret, additional, Gladysheva, Tatiana, additional, Holley, Stephanie, additional, Keefe, Kelly, additional, Kothe, Michael, additional, Lam, Becky, additional, Lim, Sungtaek, additional, Liu, Jinyu, additional, Ma, Liang, additional, Metz, Markus, additional, Scholte, Andrew A., additional, Shum, Patrick, additional, Wei, LinLi, additional, Woodworth, Lisa, additional, and Edling, Andrea, additional

Published
2024
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3. Megahertz serial crystallography

Author

Wiedorn, Max O, Oberthür, Dominik, Bean, Richard, Schubert, Robin, Werner, Nadine, Abbey, Brian, Aepfelbacher, Martin, Adriano, Luigi, Allahgholi, Aschkan, Al-Qudami, Nasser, Andreasson, Jakob, Aplin, Steve, Awel, Salah, Ayyer, Kartik, Bajt, Saša, Barák, Imrich, Bari, Sadia, Bielecki, Johan, Botha, Sabine, Boukhelef, Djelloul, Brehm, Wolfgang, Brockhauser, Sandor, Cheviakov, Igor, Coleman, Matthew A, Cruz-Mazo, Francisco, Danilevski, Cyril, Darmanin, Connie, Doak, R Bruce, Domaracky, Martin, Dörner, Katerina, Du, Yang, Fangohr, Hans, Fleckenstein, Holger, Frank, Matthias, Fromme, Petra, Gañán-Calvo, Alfonso M, Gevorkov, Yaroslav, Giewekemeyer, Klaus, Ginn, Helen Mary, Graafsma, Heinz, Graceffa, Rita, Greiffenberg, Dominic, Gumprecht, Lars, Göttlicher, Peter, Hajdu, Janos, Hauf, Steffen, Heymann, Michael, Holmes, Susannah, Horke, Daniel A, Hunter, Mark S, Imlau, Siegfried, Kaukher, Alexander, Kim, Yoonhee, Klyuev, Alexander, Knoška, Juraj, Kobe, Bostjan, Kuhn, Manuela, Kupitz, Christopher, Küpper, Jochen, Lahey-Rudolph, Janine Mia, Laurus, Torsten, Le Cong, Karoline, Letrun, Romain, Xavier, P Lourdu, Maia, Luis, Maia, Filipe RNC, Mariani, Valerio, Messerschmidt, Marc, Metz, Markus, Mezza, Davide, Michelat, Thomas, Mills, Grant, Monteiro, Diana CF, Morgan, Andrew, Mühlig, Kerstin, Munke, Anna, Münnich, Astrid, Nette, Julia, Nugent, Keith A, Nuguid, Theresa, Orville, Allen M, Pandey, Suraj, Pena, Gisel, Villanueva-Perez, Pablo, Poehlsen, Jennifer, Previtali, Gianpietro, Redecke, Lars, Riekehr, Winnie Maria, Rohde, Holger, Round, Adam, Safenreiter, Tatiana, Sarrou, Iosifina, Sato, Tokushi, Schmidt, Marius, Schmitt, Bernd, Schönherr, Robert, Schulz, Joachim, Sellberg, Jonas A, Seibert, M Marvin, and Seuring, Carolin

Subjects
Biochemistry and Cell Biology, Chemical Sciences, Biological Sciences
Abstract

The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a β-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.

Published
2018

4. Structural enzymology using X-ray free electron lasers

Author

Kupitz, Christopher, Olmos, Jose L, Holl, Mark, Tremblay, Lee, Pande, Kanupriya, Pandey, Suraj, Oberthür, Dominik, Hunter, Mark, Liang, Mengning, Aquila, Andrew, Tenboer, Jason, Calvey, George, Katz, Andrea, Chen, Yujie, Wiedorn, Max O, Knoska, Juraj, Meents, Alke, Majriani, Valerio, Norwood, Tyler, Poudyal, Ishwor, Grant, Thomas, Miller, Mitchell D, Xu, Weijun, Tolstikova, Aleksandra, Morgan, Andrew, Metz, Markus, Martin-Garcia, Jose M, Zook, James D, Roy-Chowdhury, Shatabdi, Coe, Jesse, Nagaratnam, Nirupa, Meza, Domingo, Fromme, Raimund, Basu, Shibom, Frank, Matthias, White, Thomas, Barty, Anton, Bajt, Sasa, Yefanov, Oleksandr, Chapman, Henry N, Zatsepin, Nadia, Nelson, Garrett, Weierstall, Uwe, Spence, John, Schwander, Peter, Pollack, Lois, Fromme, Petra, Ourmazd, Abbas, Phillips, George N, and Schmidt, Marius

Subjects
Inorganic Chemistry, Chemical Sciences, Physical Sciences, Infectious Diseases, Good Health and Well Being, Physical chemistry, Condensed matter physics, Particle and high energy physics
Abstract

Mix-and-inject serial crystallography (MISC) is a technique designed to image enzyme catalyzed reactions in which small protein crystals are mixed with a substrate just prior to being probed by an X-ray pulse. This approach offers several advantages over flow cell studies. It provides (i) room temperature structures at near atomic resolution, (ii) time resolution ranging from microseconds to seconds, and (iii) convenient reaction initiation. It outruns radiation damage by using femtosecond X-ray pulses allowing damage and chemistry to be separated. Here, we demonstrate that MISC is feasible at an X-ray free electron laser by studying the reaction of M. tuberculosis ß-lactamase microcrystals with ceftriaxone antibiotic solution. Electron density maps of the apo-ß-lactamase and of the ceftriaxone bound form were obtained at 2.8 Å and 2.4 Å resolution, respectively. These results pave the way to study cyclic and non-cyclic reactions and represent a new field of time-resolved structural dynamics for numerous substrate-triggered biological reactions.

Published
2017

5. Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein

Author

Pande, Kanupriya, Hutchison, Christopher DM, Groenhof, Gerrit, Aquila, Andy, Robinson, Josef S, Tenboer, Jason, Basu, Shibom, Boutet, Sébastien, DePonte, Daniel P, Liang, Mengning, White, Thomas A, Zatsepin, Nadia A, Yefanov, Oleksandr, Morozov, Dmitry, Oberthuer, Dominik, Gati, Cornelius, Subramanian, Ganesh, James, Daniel, Zhao, Yun, Koralek, Jake, Brayshaw, Jennifer, Kupitz, Christopher, Conrad, Chelsie, Roy-Chowdhury, Shatabdi, Coe, Jesse D, Metz, Markus, Xavier, Paulraj Lourdu, Grant, Thomas D, Koglin, Jason E, Ketawala, Gihan, Fromme, Raimund, Šrajer, Vukica, Henning, Robert, Spence, John CH, Ourmazd, Abbas, Schwander, Peter, Weierstall, Uwe, Frank, Matthias, Fromme, Petra, Barty, Anton, Chapman, Henry N, Moffat, Keith, van Thor, Jasper J, and Schmidt, Marius

Subjects
Biological Sciences, Chemical Sciences, Theoretical and Computational Chemistry, Bacterial Proteins, Crystallography, Isomerism, Light, Photochemical Processes, Photons, Photoreceptors, Microbial, Protein Conformation, Time Factors, General Science & Technology
Abstract

A variety of organisms have evolved mechanisms to detect and respond to light, in which the response is mediated by protein structural changes after photon absorption. The initial step is often the photoisomerization of a conjugated chromophore. Isomerization occurs on ultrafast time scales and is substantially influenced by the chromophore environment. Here we identify structural changes associated with the earliest steps in the trans-to-cis isomerization of the chromophore in photoactive yellow protein. Femtosecond hard x-ray pulses emitted by the Linac Coherent Light Source were used to conduct time-resolved serial femtosecond crystallography on photoactive yellow protein microcrystals over a time range from 100 femtoseconds to 3 picoseconds to determine the structural dynamics of the photoisomerization reaction.

Published
2016

7. Robust evidence for bats as reservoir hosts is lacking in most African virus studies: a review and call to optimize sampling and conserve bats

Author

Weber, Natalie, primary, Nagy, Martina, additional, Markotter, Wanda, additional, Schaer, Juliane, additional, Puechmaille, Sébastien J., additional, Sutton, Jack, additional, Dávalos, Liliana M., additional, Dusabe, Marie-Claire, additional, Ejotre, Imran, additional, Fenton, M. Brock, additional, Knörnschild, Mirjam, additional, López-Baucells, Adrià, additional, Medellin, Rodrigo A., additional, Metz, Markus, additional, Mubareka, Samira, additional, Nsengimana, Olivier, additional, O'Mara, M. Teague, additional, Racey, Paul A., additional, Tuttle, Merlin, additional, Twizeyimana, Innocent, additional, Vicente-Santos, Amanda, additional, Tschapka, Marco, additional, Voigt, Christian C., additional, Wikelski, Martin, additional, Dechmann, Dina K.N., additional, and Reeder, DeeAnn M., additional

Published
2023
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11. Using EO parameters to model Vector Diseases and their drivers (MOOD project @ ESA Living Planet Symposium 2022)

Author

Neteler, Markus, Haas, Julia, Metz, Markus, Koess, Veronica, Halbauer, Johannes, Alexander, Neil, and Wint, William

Subjects
Europe, epidemic intelligence, model, risk assessment, covariate data, MOOD-H2020, vector borne, diseases
Abstract

Overview: The H2020 MOOD project (Web site; CORDIS) is focused on using ‘big data’ to provide risk assessments to Public Health professionals for a range of diseases including many Vector Borne Diseases such as Dengue, Tick Borne Encephalitis, West Nile Fever, and Congo Crimean Hemorrhagic Fever. Producing these risk assessments requires substantial support to provide the covariate datasets that drive the disease models. These datasets span a wide range of types of information, ranging from demographic, socio-economic and agricultural information to Earth Observation (EO) imagery. This last set of environmental and climatic parameters are derived from a variety of EO and terrestrial sources , and comprise both near real time and long-term synoptic summaries produced by data reduction techniques such as Temporal Fourier Analysis of extensive time series of decadal imagery. The distributions of both disease vectors and hosts are also produced as additional drivers, either using species aggregation protocols, or estimated by spatial distribution modelling employing machine learning techniques and ensembling the outputs of several methods. The project includes dedicated work packages to identify source, acquire, process, and supply the covariate datasets that drive the disease models to the modelers within the project as well as to external users that have requested access to such data. The presentation provides an overview of these data streams and driver modelling modelling techniques, taking examples from a number of diseases. These procedures include not only the driver modelling, but also parameter identification and selection, variable data reduction, static and dynamic suitability definition and masking, and data dissemination. The presentation also discusses the particular requirements of providing such information to both the modellers, and to external users in the Public health arena who often need the products produced by academic research teams as publishable outputs to be adapted and adjusted for more practically oriented use, as well as made accessible in formats more suited to risk assessments than raster images., Acknowledgements: This work has been partially founded by the European Union's Horizon 2020 research and innovation programme under Grant Agreement MOOD 874850.

Published
2022
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13. Uncertainty in ecosystem mapping by remote sensing

Author

Rocchini, Duccio, Foody, Giles M., Nagendra, Harini, Ricotta, Carlo, Anand, Madhur, He, Kate S., Amici, Valerio, Kleinschmit, Birgit, Förster, Michael, Schmidtlein, Sebastian, Feilhauer, Hannes, Ghisla, Anne, Metz, Markus, and Neteler, Markus

Published
2013
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23. PROTEIN STRUCTURE: Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein

Author

Pande, Kanupriya, Hutchison, Christopher D. M., Groenhof, Gerrit, Aquila, Andy, Robinson, Josef S., Tenboer, Jason, Basu, Shibom, Boutet, Sébastien, DePonte, Daniel P., Liang, Mengning, White, Thomas A., Zatsepin, Nadia A., Yefanov, Oleksandr, Morozov, Dmitry, Oberthuer, Dominik, Gati, Cornelius, Subramanian, Ganesh, James, Daniel, Zhao, Yun, Koralek, Jake, Brayshaw, Jennifer, Kupitz, Christopher, Conrad, Chelsie, Roy-Chowdhury, Shatabdi, Coe, Jesse D., Metz, Markus, Xavier, Paulraj Lourdu, Grant, Thomas D., Koglin, Jason E., Ketawala, Gihan, Fromme, Raimund, Šrajer, Vukica, Henning, Robert, Spence, John C. H., Ourmazd, Abbas, Schwander, Peter, Weierstall, Uwe, Frank, Matthias, Fromme, Petra, Barty, Anton, Chapman, Henry N., Moffat, Keith, van Thor, Jasper J., and Schmidt, Marius

Published
2016
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24. Macromolecular diffractive imaging using imperfect crystals

Author

Ayyer, Kartik, Yefanov, Oleksandr M., Oberthür, Dominik, Roy-Chowdhury, Shatabdi, Galli, Lorenzo, Mariani, Valerio, Basu, Shibom, Coe, Jesse, Conrad, Chelsie E., Fromme, Raimund, Schaffer, Alexander, Dörner, Katerina, James, Daniel, Kupitz, Christopher, Metz, Markus, Nelson, Garrett, Xavier, Paulraj Lourdu, Beyerlein, Kenneth R., Schmidt, Marius, Sarrou, Iosifina, Spence, John C. H., Weierstall, Uwe, White, Thomas A., Yang, Jay-How, Zhao, Yun, Liang, Mengning, Aquila, Andrew, Hunter, Mark S., Robinson, Joseph S., Koglin, Jason E., Boutet, Sébastien, Fromme, Petra, Barty, Anton, and Chapman, Henry N.

Published
2016
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25. Macromolecular phasing using diffraction from multiple crystal forms

Author

Metz, Markus, Arnal, Romain D., Brehm, Wolfgang, Chapman, Henry N., Morgan, Andrew J., and Millane, Rick P.

Subjects
Quantitative Biology::Biomolecules, XFELs, iterative projection algorithms, ab initio phasing, Physics::Optics, X-ray free-electron lasers, ddc:530, Research Papers, multiple crystal forms
Abstract

Acta crystallographica / A 77(1), 19 - 35 (2021). doi:10.1107/S2053273320013650, A phasing algorithm for macromol��ecular crystallography is proposed that utilizes diffraction data from multiple crystal forms ��� crystals of the same mol��ecule with different unit-cell packings (different unit-cell parameters or space-group symmetries). The approach is based on the method of iterated projections, starting with no initial phase information. The practicality of the method is demonstrated by simulation using known structures that exist in multiple crystal forms, assuming some information on the mol��ecular envelope and positional relationships between the mol��ecules in the different unit cells. With incorporation of new or existing methods for determination of these parameters, the approach has potential as a method for ab initio phasing., Published by Blackwell, Oxford [u.a.]

Published
2021

29. Baboon responses to graded bark variants

Author

Fischer, Julia, Metz, Markus, Cheney, Dorothy L., and Seyfarth, Robert M.

Subjects
Baboons -- Behavior, Sound production by animals -- Research, Zoology and wildlife conservation
Abstract

A new study of free-ranging chacma baboons, Papio cynocephalus ursinus, investigates their responses to conspecific barks.

Published
2001

32. Evaluation of serial crystallographic structure determination within megahertz pulse trains

Author

Yefanov, Oleksandr, primary, Oberthür, Dominik, additional, Bean, Richard, additional, Wiedorn, Max O., additional, Knoska, Juraj, additional, Pena, Gisel, additional, Awel, Salah, additional, Gumprecht, Lars, additional, Domaracky, Martin, additional, Sarrou, Iosifina, additional, Lourdu Xavier, P., additional, Metz, Markus, additional, Bajt, Saša, additional, Mariani, Valerio, additional, Gevorkov, Yaroslav, additional, White, Thomas A., additional, Tolstikova, Aleksandra, additional, Villanueva-Perez, Pablo, additional, Seuring, Carolin, additional, Aplin, Steve, additional, Estillore, Armando D., additional, Küpper, Jochen, additional, Klyuev, Alexander, additional, Kuhn, Manuela, additional, Laurus, Torsten, additional, Graafsma, Heinz, additional, Monteiro, Diana C. F., additional, Trebbin, Martin, additional, Maia, Filipe R. N. C., additional, Cruz-Mazo, Francisco, additional, Gañán-Calvo, Alfonso M., additional, Heymann, Michael, additional, Darmanin, Connie, additional, Abbey, Brian, additional, Schmidt, Marius, additional, Fromme, Petra, additional, Giewekemeyer, Klaus, additional, Sikorski, Marcin, additional, Graceffa, Rita, additional, Vagovic, Patrik, additional, Kluyver, Thomas, additional, Bergemann, Martin, additional, Fangohr, Hans, additional, Sztuk-Dambietz, Jolanta, additional, Hauf, Steffen, additional, Raab, Natascha, additional, Bondar, Valerii, additional, Mancuso, Adrian P., additional, Chapman, Henry, additional, and Barty, Anton, additional

Published
2019
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33. Evaluation of serial crystallographic structure determination within megahertz pulse trains

Author

Yefanov, Oleksandr, Oberthür, Dominik, Bean, Richard, Wiedorn, Max O., Knoska, Juraj, Pena, Gisel, Awel, Salah, Domaracky, Martin, Sarrou, Iosifina, Lourdu Xavier, P., Metz, Markus, Bajt, Saša, Mariani, Valerio, Gevorkov, Yaroslav, White, Thomas A., Tolstikova, Aleksandra, Villanueva-Pérez, Pablo, Seuring, Carolin, Aplin, Steve, Estillore, Armando D., Küpper, Jochen, Klyuev, Alexander, Kuhn, Manuela, Laurus, Torsten, Graafsma, Heinz, Monteiro, Diana C. F., Trebbin, Martin, Maia, Filipe R. N. C., Cruz-Mazo, Francisco, Gañán-Calvo, Alfonso M., Universidad de Sevilla. Departamento de Ingeniería Aeroespacial y Mecánica de Fluidos, and Universidad de Sevilla. TEP 219 : Física de Fluidos y Microfluidica

Subjects
Free Electron Lasers, Crystallography, X-Ray Laser
Abstract

The new European X-ray Free-Electron Laser (European XFEL) is the first X-ray free-electron laser capable of delivering intense X-ray pulses with a megahertz interpulse spacing in a wavelength range suitable for atomic resolution structure determination. An outstanding but crucial question is whether the use of a pulse repetition rate nearly four orders of magnitude higher than previously possible results in unwanted structural changes due to either radiation damage or systematic effects on data quality. Here, separate structures from the first and subse- quent pulses in the European XFEL pulse train were determined, showing that there is essentially no difference between structures deter- mined from different pulses under currently available operating conditions at the European XFEL.

Published
2019

34. Synthesis and structure of Pd4(mu-PtBu2)2(mu-CS2)(PPh3)2I2, a neutral palladium(I) derivative with a hexacoordinate carbon and a CS2 molecule bridging four palladium centers

Author

Leoni, Piero, Pasquali, Marco, Fadini, LUca, Albinati, Alberto, Hofmann, Peter, and Metz, Markus

Subjects
Organic compounds -- Observations, Palladium catalysts -- Observations, Chemical reactions -- Observations, Chemistry
Abstract

CS2 complex (Pd2(muPtBu2)(mu,eta2:eta2-CS2)(PPh3)2)BF4, BF4, reacted with Me4NI, yielding the neutral tetranuclear Pd(I) derivative Pd4(mu-PtBu2)2(mu4-CS2)(PPh3)2I, characterized by single crystal X-ray diffraction. The unusual molecular structure, with a formally hexacoordinate carbon atom, is explained on the basis of fragment MO considerations and EHMO models. The stepwise reaction proceeds with a fast substitution of CS2 by the iodide ion.

Published
1997

38. Mix-and-diffuse serial synchrotron crystallography

Author

Beyerlein, Kenneth R., Dierksmeyer, Dennis, Mariani, Valerio, Kuhn, Manuela, Sarrou, Iosifina, Ottaviano, Angelica, Awel, Salah, Knoska, Juraj, Fuglerud, Silje Skeide, Jönsson, Olof, Stern, Stephan, Wiedorn, Max O., Yefanov, Oleksandr, Adriano, Luigi, Bean, Richard, Burkhardt, Anja, Fischer, Pontus, Heymann, Michael, Horke, Daniel A., Jungnickel, Katharina E.J., Kovaleva, Elena, Lorbeer, Olga, Metz, Markus, Meyer, Jan, Morgan, Andrew, Pande, Kanupriya, Panneerselvam, Saravanan, Seuring, Carolin, Tolstikova, Aleksandra, Lieske, Julia, Aplin, Steve, Roessle, Manfred, White, Thomas A., Chapman, Henry N., Meents, Alke, and Oberthuer, Dominik

Subjects
Materials Chemistry, Materialkemi, lcsh:Q, serial crystallography, ddc:530, protein structure, lcsh:Science, Research Papers, lysozyme, time-resolved studies, drug discovery, X-ray crystallography
Abstract

The structure of chitotriose bound to lysozyme after mixing times of 2 and 50 s was determined using a polyimide tape-drive device for mix-and-diffuse serial crystallography at a synchrotron light source., Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzyme at a high level of detail. The success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.

Published
2017

39. Mathematical and Structural Characterization of Strong Nonadditive Structure–Activity Relationship Caused by Protein Conformational Changes

Author

Gomez, Laurent, primary, Xu, Rui, additional, Sinko, William, additional, Selfridge, Brandon, additional, Vernier, William, additional, Ly, Kiev, additional, Truong, Richard, additional, Metz, Markus, additional, Marrone, Tami, additional, Sebring, Kristen, additional, Yan, Yingzhou, additional, Appleton, Brent, additional, Aertgeerts, Kathleen, additional, Massari, Mark Eben, additional, and Breitenbucher, J. Guy, additional

Published
2018
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41. Mix-and-diffuse serial synchrotron crystallography

Author

Beyerlein, Kenneth R., primary, Dierksmeyer, Dennis, additional, Mariani, Valerio, additional, Kuhn, Manuela, additional, Sarrou, Iosifina, additional, Ottaviano, Angelica, additional, Awel, Salah, additional, Knoska, Juraj, additional, Fuglerud, Silje, additional, Jönsson, Olof, additional, Stern, Stephan, additional, Wiedorn, Max O., additional, Yefanov, Oleksandr, additional, Adriano, Luigi, additional, Bean, Richard, additional, Burkhardt, Anja, additional, Fischer, Pontus, additional, Heymann, Michael, additional, Horke, Daniel A., additional, Jungnickel, Katharina E. J., additional, Kovaleva, Elena, additional, Lorbeer, Olga, additional, Metz, Markus, additional, Meyer, Jan, additional, Morgan, Andrew, additional, Pande, Kanupriya, additional, Panneerselvam, Saravanan, additional, Seuring, Carolin, additional, Tolstikova, Aleksandra, additional, Lieske, Julia, additional, Aplin, Steve, additional, Roessle, Manfred, additional, White, Thomas A., additional, Chapman, Henry N., additional, Meents, Alke, additional, and Oberthuer, Dominik, additional

Published
2017
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43. Additional file 1: of First assessment of potential distribution and dispersal capacity of the emerging invasive mosquito Aedes koreicus in Northeast Italy

Author

Marcantonio, Matteo, Metz, Markus, FrĂŠdĂŠric Baldacchino, Arnoldi, Daniele, Montarsi, Fabrizio, Capelli, Gioia, Carlin, Sara, Neteler, Markus, and Annapaola Rizzoli

Abstract

Title of data: R function to perform logistic regression with Bayesian inference. Description of data: R function to perform logistic regression with Bayesian inference. (PDF 37 kb)

Published
2016
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46. Design and Synthesis of Novel and Selective Phosphodiesterase 2 (PDE2a) Inhibitors for the Treatment of Memory Disorders

Author

Gomez, Laurent, primary, Massari, Mark Eben, additional, Vickers, Troy, additional, Freestone, Graeme, additional, Vernier, William, additional, Ly, Kiev, additional, Xu, Rui, additional, McCarrick, Margaret, additional, Marrone, Tami, additional, Metz, Markus, additional, Yan, Yingzhou G., additional, Yoder, Zachary W., additional, Lemus, Robert, additional, Broadbent, Nicola J., additional, Barido, Richard, additional, Warren, Noelle, additional, Schmelzer, Kara, additional, Neul, David, additional, Lee, Dong, additional, Andersen, Carsten B., additional, Sebring, Kristen, additional, Aertgeerts, Kathleen, additional, Zhou, Xianbo, additional, Tabatabaei, Ali, additional, Peters, Marco, additional, and Breitenbucher, J. Guy, additional

Published
2017
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47. Structural enzymology using X-ray free electron lasers

Author

Kupitz, Christopher, primary, Olmos, Jose L., additional, Holl, Mark, additional, Tremblay, Lee, additional, Pande, Kanupriya, additional, Pandey, Suraj, additional, Oberthür, Dominik, additional, Hunter, Mark, additional, Liang, Mengning, additional, Aquila, Andrew, additional, Tenboer, Jason, additional, Calvey, George, additional, Katz, Andrea, additional, Chen, Yujie, additional, Wiedorn, Max O., additional, Knoska, Juraj, additional, Meents, Alke, additional, Majriani, Valerio, additional, Norwood, Tyler, additional, Poudyal, Ishwor, additional, Grant, Thomas, additional, Miller, Mitchell D., additional, Xu, Weijun, additional, Tolstikova, Aleksandra, additional, Morgan, Andrew, additional, Metz, Markus, additional, Martin-Garcia, Jose M., additional, Zook, James D., additional, Roy-Chowdhury, Shatabdi, additional, Coe, Jesse, additional, Nagaratnam, Nirupa, additional, Meza, Domingo, additional, Fromme, Raimund, additional, Basu, Shibom, additional, Frank, Matthias, additional, White, Thomas, additional, Barty, Anton, additional, Bajt, Sasa, additional, Yefanov, Oleksandr, additional, Chapman, Henry N., additional, Zatsepin, Nadia, additional, Nelson, Garrett, additional, Weierstall, Uwe, additional, Spence, John, additional, Schwander, Peter, additional, Pollack, Lois, additional, Fromme, Petra, additional, Ourmazd, Abbas, additional, Phillips, George N., additional, and Schmidt, Marius, additional

Published
2016
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48. Specificity for a CCR5 Inhibitor Is Conferred by a Single Amino Acid Residue: ROLE OF ILE198

Author

Lau, Gloria, Labrecque, Jean, Metz, Markus, Vaz, Roy, and Fricker, Simon P.

Subjects
Models, Molecular, Receptors, CCR5, Receptors, CCR2, Recombinant Fusion Proteins, fungi, food and beverages, virus diseases, Computational Biology, Amides, Protein Structure, Tertiary, Quaternary Ammonium Compounds, HEK293 Cells, CCR5 Receptor Antagonists, Animals, Humans, Macaca, Amino Acid Sequence, Calcium Signaling, Isoleucine
Abstract

The chemokine receptors CCR5 and CCR2b share 89% amino acid homology. CCR5 is a co-receptor for HIV and CCR5 antagonists have been investigated as inhibitors of HIV infection. We describe the use of two CCR5 antagonists, Schering-C (SCH-C), which is specific for CCR5, and TAK-779, a dual inhibitor of CCR5 and CCR2b, to probe the CCR5 inhibitor binding site using CCR5/CCR2b chimeric receptors. Compound inhibition in the different chimeras was assessed by inhibition of chemokine-induced calcium flux. SCH-C inhibited RANTES (regulated on activation, normal T cell expressed and secreted) (CCL5)-mediated calcium flux on CCR5 with an IC50 of 22.8 nM but was inactive against monocyte chemoattractant protein-1 (CCL2)-mediated calcium flux on CCR2b. However, SCH-C inhibited CCL2-induced calcium flux against a CCR5/CCR2b chimera consisting of transmembrane domains IV-VI of CCR5 with an IC50 of 55 nM. A sequence comparison of CCR5 and CCR2b identified a divergent amino acid sequence located at the junction of transmembrane domain V and second extracellular loop. Transfer of the CCR5 sequence KNFQTLKIV into CCR2b conferred SCH-C inhibition (IC50 of 122 nM) into the predominantly CCR2b chimera. Furthermore, a single substitution, R206I, conferred partial but significant inhibition (IC50 of 1023 nM) by SCH-C. These results show that a limited amino acid sequence is responsible for SCH-C specificity to CCR5, and we propose a model showing the interaction with CCR5 Ile(198).

Published
2015

49. Structural basis for bifunctional peptide recognition at human delta-opioid receptor. IF 13.338

Author

Fenalti, Gustavo, Zatsepin, Nadia, Betti, Cecilia, Giguere, Patrick, Han, Gye Won, Ishchenko, Andrii, Liu, Wei, Guillemyn, Karel, Zhang, Haitao, James, Daniel, Wang, Dingjie, Weierstall, Uwe, Spence, John CH, Boutet, Sébastien, Messerschmidt, Marc, Williams, Garth J, Gati, Cornelius, Yefanov, Oleksandr M, White, Thomas A, Oberthuer, Dominik, Metz, Markus, Yoon, Chun Hong, Barty, Anton, Chapman, Henry N, Basu, Shibom, Coe, Jesse, Conrad, Chelsie E, Fromme, Raimund, Fromme, Petra, Tourwe, Dirk, Schiller, Peter, Roth, Bryan L, Ballet, Steven, Katritch, Vsevolod, Stevens, Raymond C, Cherezov, Vadim, Chemistry, Faculty of Sciences and Bioengineering Sciences, and Organic Chemistry

Subjects
SERIAL FEMTOSECOND CRYSTALLOGRAPHY, MU AGONIST/DELTA ANTAGONIST, POTENT, TOLERANCE, DEPENDENCE, MORPHINE, BOND, DMT
Abstract

Bifunctional mu- and delta-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human delta-OR bound to the bifunctional delta-OR antagonist and mu-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics.

Published
2015

50. Serial femtosecond crystallography datasets from G protein-coupled receptors

Author

White, Thomas A., primary, Barty, Anton, additional, Liu, Wei, additional, Ishchenko, Andrii, additional, Zhang, Haitao, additional, Gati, Cornelius, additional, Zatsepin, Nadia A., additional, Basu, Shibom, additional, Oberthür, Dominik, additional, Metz, Markus, additional, Beyerlein, Kenneth R., additional, Yoon, Chun Hong, additional, Yefanov, Oleksandr M., additional, James, Daniel, additional, Wang, Dingjie, additional, Messerschmidt, Marc, additional, Koglin, Jason E., additional, Boutet, Sébastien, additional, Weierstall, Uwe, additional, and Cherezov, Vadim, additional

Published
2016
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