| 1. |
- Andersson, B, et al.
(författare)
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Crystallization and X-ray diffraction data analysis of leukotriene A4 hydrolase from Saccharomyces cerevisiae
- 2003
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; D59:Pt 6, s. 1093-1095
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Tidskriftsartikel (refereegranskat)abstract
- The Saccharomyces cerevisiae leukotriene A4 (LTA4) hydrolase (scLTA4 hydrolase) has been crystallized in order to study the two activities of LTA4 hydrolase in an evolutionary perspective. Single well diffracting crystals are obtained after switching from the hanging-drop method to liquid-liquid diffusion in capillaries using PEG 8000 as precipitant. These crystals belong to space group P212121, with unit-cell parameters a = 70.8, b = 98.1, c = 99.2 Å. Intensity data to 2.3 Å resolution were collected from a native scLTA4 hydrolase crystal using synchrotron radiation. A molecular-replacement solution was obtained using the human LTA4 hydrolase structure and the program BEAST.
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| 2. |
- Awad, Wael, et al.
(författare)
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Improvements in the order, isotropy and electron density of glypican-1 crystals by controlled dehydration.
- 2013
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; 69:Pt 12, s. 2524-2533
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Tidskriftsartikel (refereegranskat)abstract
- The use of controlled dehydration for improvement of protein crystal diffraction quality is increasing in popularity, although there are still relatively few documented examples of success. A study has been carried out to establish whether controlled dehydration could be used to improve the anisotropy of crystals of the core protein of the human proteoglycan glypican-1. Crystals were subjected to controlled dehydration using the HC1 device. The optimal protocol for dehydration was developed by careful investigation of the following parameters: dehydration rate, final relative humidity and total incubation time Tinc. Of these, the most important was shown to be Tinc. After dehydration using the optimal protocol the crystals showed significantly reduced anisotropy and improved electron density, allowing the building of previously disordered parts of the structure.
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| 3. |
- Bowler, Matthew W., et al.
(författare)
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Automation and Experience of Controlled Crystal Dehydration: Results from the European Synchrotron HC1 Collaboration
- 2015
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 15:3, s. 1043-1054
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Tidskriftsartikel (refereegranskat)abstract
- Controlled dehydration of macromolecular crystals can lead to significant improvements in crystalline order, which often manifests itself in higher diffraction quality. Devices that can accurately control the humidity surrounding crystals on a beamline have led to this technique being increasingly adopted as experiments become easier and more reproducible. However, these experiments are often carried out by trial and error, and in order to facilitate and streamline them four European synchrotrons have established a collaboration around the HC1b dehydration device. The MAX IV Laboratory, Diamond Light Source, BESSY II, and the EMBL Grenoble Outstation/ESRF have pooled information gathered from user experiments, and on the use of the device, to propose a set of guidelines for these experiments. Here, we present the status and automation of the installations, advice on how best to perform experiments using the device, and an analysis of successful experiments that begins to show some trends in the type of protocols required by some systems. The dehydration methods shown are applicable to any device that allows control of the relative humidity of the air surrounding a macromolecular crystal.
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| 4. |
- Helgstrand, Charlotte, et al.
(författare)
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A Leukotriene A(4) Hydrolase-Related Aminopeptidase from Yeast Undergoes Induced Fit upon Inhibitor Binding.
- 2011
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 406, s. 120-134
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Tidskriftsartikel (refereegranskat)abstract
- Vertebrate leukotriene A(4) hydrolases are bifunctional zinc metalloenzymes with an epoxide hydrolase and an aminopeptidase activity. In contrast, highly homologous enzymes from lower organisms only have the aminopeptidase activity. From sequence comparisons, it is not clear why this difference occurs. In order to obtain more information on the evolutionary relationship between these enzymes and their activities, the structure of a closely related leucine aminopeptidase from Saccharomyces cerevisiae that only shows a very low epoxide hydrolase activity was determined. To investigate the molecular architecture of the active site, the structures of both the native protein and the protein in complex with the aminopeptidase inhibitor bestatin were solved. These structures show a more spacious active site, and the protected cavity in which the labile substrate leukotriene A(4) is bound in the human enzyme is partially obstructed and in other parts is more solvent accessible. Furthermore, the enzyme undergoes induced fit upon binding of the inhibitor bestatin, leading to a movement of the C-terminal domain. The main triggers for the domain movement are a conformational change of Tyr312 and a subtle change in backbone conformation of the PYGAMEN fingerprint region for peptide substrate recognition. This leads to a change in the hydrogen-bonding network pulling the C-terminal domain into a different position. Inasmuch as bestatin is a structural analogue of a leucyl dipeptide and may be regarded as a transition state mimic, our results imply that the enzyme undergoes induced fit during substrate binding and turnover.
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| 5. |
- Johansson, Ulf, et al.
(författare)
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MAX IV is Ready to Make the Invisible Visible
- 2016
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Ingår i: Synchrotron Radiation News. - : Informa UK Limited. - 0894-0886 .- 1931-7344. ; 29:6, s. 16-25
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Forskningsöversikt (refereegranskat)abstract
- In a ceremony held on June 21, the brightest day of the year in the northern hemisphere, Swedish Prime Minister Stefan Löfven and H.M. King Carl XVI Gustaf, together with Director Christoph Quitmann, inaugurated MAX IV Laboratory in the presence of about 500 staff, funders, stakeholders, and guests from all over the world.
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| 6. |
- Kirkland, Thomas A., et al.
(författare)
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Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A(4) hydrolase
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 16:9, s. 4963-4983
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Tidskriftsartikel (refereegranskat)abstract
- Leukotriene B-4 (LTB4) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB4 and possibly identify novel treatments, inhibitors of the LTB4 biosynthetic enzyme, leukotriene A(4) hydrolase (LTA(4)-h), have been explored. Here we describe the discovery of a potent inhibitor of LTA(4)-h, arylamide of glutamic acid 4f, starting from the corresponding glycinamide 2. Analogs of 4f are then described, focusing on compounds that are both active and stable in whole blood. This effort culminated in the identification of amino alcohol 12a and amino ester 6b which meet these criteria.
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| 7. |
- Lindkvist, Karin, et al.
(författare)
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Crystal structure of a SEA variant in complex with MHC class II reveals the ability of SEA to crosslink MHC molecules
- 2002
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Ingår i: Structure. - 0969-2126. ; 10:12, s. 1619-1626
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Tidskriftsartikel (refereegranskat)abstract
- Although the biological properties of staphylococcal enterotoxin A (SEA) have been well characterized, structural insights into the interaction between SEA and major histocompatibilty complex (MHC) class II have only been obtained by modeling. Here, the crystal structure of the D227A variant of SEA in complex with human MHC class II has been determined by X-ray crystallography. SEA(D227A) exclusively binds with its N-terminal domain to the alpha chain of HLA-DR1. The ability of one SEA molecule to crosslink two MHC molecules was modeled. It shows that this SEA molecule cannot interact with the T cell receptor (TCR) while a second SEA molecule interacts with MHC. Because of its relatively low toxicity, the D227A variant of SEA is used in tumor therapy.
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| 8. |
- Logan, Derek, et al.
(författare)
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Status of the crystallography beamlines at the MAX IV Laboratory
- 2015
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Ingår i: The European Physical Journal Plus. - : Springer Science and Business Media LLC. - 2190-5444. ; 130:3
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Forskningsöversikt (refereegranskat)abstract
- The MAX IV Laboratory in Lund is currently operating two storage rings, the 1.5 GeV MAX II and the 700MeV MAX III, as well as constructing the new facility MAX IV, which will house a 1.5 GeV and a 3 GeV ring. At the MAX II synchrotron there are three hard X-ray beamlines at which crystallography can be performed: I711, I811 and I911. Beamline I711 is mainly used for powder diffraction. I811 is an EXAFS station at which surface XRD can also be carried out. I911 is a beamline with five experimental stations on a single superconducting wiggler source, of which two are currently used for macromolecular crystallography, namely the monochromatic station I911-2 and the tuneable station I911-3, which is equipped with a state-of-the-art goniometer and robotic sample changer. We will give an overview of the capabilities of these beamlines, focusing particularly on the macromolecular crystallography beamline I911 and some recent scientific highlights produced there. We will also give a brief overview of new beamlines for crystallography that are under construction or planned for the MAX IV facility.
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| 9. |
- Mammen, C.B., et al.
(författare)
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Bent Diamond Crystals and Multilayer Based Optics at the new 5-Station Protein Crystallography Beamline ‘Cassiopeia’ at MAX-lab
- 2004
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Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. - 0735401799 ; 705:1, s. 808-811
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Konferensbidrag (refereegranskat)abstract
- A new 5-station beamline for protein crystallography is being commissioned at the Swedish synchrotron light source MAX-II at Lund University. Of the 2K/gamma = 14 mrad horizontal wiggler fan, the central 2 mrad are used and split in three parts. The central 1 mrad will be used for a station optimized for MAD experiments and on each side of the central fan, from 0.5 mrad to 1 mrad, there are two fixed energy stations using different energies of the same part of the beam. These, in total five stations, can be used simultaneously and independently for diffraction data collection. The two upstream monochromators for the side stations are meridionally bent asymmetric diamond(111) crystals in Laue transmission geometry. The monochromators for the downstream side stations are bent Ge(111) crystals in asymmetric Bragg reflection geometry. Curved multilayer mirrors inserted in the monochromatic beams provide focusing in the vertical plane. The first side station is under commissioning, and a preliminary test protein data set has been collected. ©2004 American Institute of Physics
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| 10. |
- Mammen, C B, et al.
(författare)
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Design of a 5-station macromolecular crystallography beamline at MAX-Lab
- 2002
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Ingår i: Acta Physica Polonica. Series A: General Physics, Physics of Condensed Matter, Optics and Quantum Electronics, Atomic and Molecular Physics, Applied Physics. - 0587-4246. ; 101:5, s. 595-602
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Tidskriftsartikel (refereegranskat)abstract
- A beamline for macromolecular crystallography is under construction at the Swedish synchrotron light source MAX-lab at Lund University in a collaborative effort between Denmark and Sweden. Of the 7 mrad horizontal wiggler fan emitted from the new superconducting multipole wiggler, the central 2 mrad will be used and split in three parts. The central 1 mrad will be used for a tunable station optimised for multi-wavelength anomalous diffraction experiments and on each side of the central fan there will be two fixed wavelength stations using different energies of the same part of the beam. These in total five stations can be used simultaneously and independently for collecting diffraction data.
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