scholarly journals Protein–ligand complex structure from serial femtosecond crystallography using soaked thermolysin microcrystals and comparison with structures from synchrotron radiation

2017 ◽  
Vol 73 (8) ◽  
pp. 702-709 ◽  
Author(s):  
Hisashi Naitow ◽  
Yoshinori Matsuura ◽  
Kensuke Tono ◽  
Yasumasa Joti ◽  
Takashi Kameshima ◽  
...  
Keyword(s):  
Synchrotron Radiation ◽  
Room Temperature ◽  
Complex Structure ◽  
Binding Mode ◽  
Ligand Complex ◽  
X Ray ◽  
Cell Parameters ◽  
Serial Femtosecond Crystallography ◽  
Small Molecule Ligand

Serial femtosecond crystallography (SFX) with an X-ray free-electron laser is used for the structural determination of proteins from a large number of microcrystals at room temperature. To examine the feasibility of pharmaceutical applications of SFX, a ligand-soaking experiment using thermolysin microcrystals has been performed using SFX. The results were compared with those from a conventional experiment with synchrotron radiation (SR) at 100 K. A protein–ligand complex structure was successfully obtained from an SFX experiment using microcrystals soaked with a small-molecule ligand; both oil-based and water-based crystal carriers gave essentially the same results. In a comparison of the SFX and SR structures, clear differences were observed in the unit-cell parameters, in the alternate conformation of side chains, in the degree of water coordination and in the ligand-binding mode.

scholarly journals Identification of the first small-molecule ligand of the neuronal receptor sortilin and structure determination of the receptor–ligand complex

2014 ◽  
Vol 70 (2) ◽  
pp. 451-460 ◽  
Author(s):  
Jacob Lauwring Andersen ◽  
Tenna Juul Schrøder ◽  
Søren Christensen ◽  
Dorthe Strandbygård ◽  
Lone Tjener Pallesen ◽  
...  
Keyword(s):  
Small Molecule ◽  
Binding Mode ◽  
Membrane Glycoprotein ◽  
Type I ◽  
Ligand Complex ◽  
Neuronal Viability ◽  
The Central Nervous System ◽  
Vacuolar Protein ◽  
Small Molecule Ligand

Sortilin is a type I membrane glycoprotein belonging to the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors and is most abundantly expressed in the central nervous system. Sortilin has emerged as a key player in the regulation of neuronal viability and has been implicated as a possible therapeutic target in a range of disorders. Here, the identification of AF40431, the first reported small-molecule ligand of sortilin, is reported. Crystals of the sortilin–AF40431 complex were obtained by co-crystallization and the structure of the complex was solved to 2.7 Å resolution. AF40431 is bound in the neurotensin-binding site of sortilin, with the leucine moiety of AF40431 mimicking the binding mode of the C-terminal leucine of neurotensin and the 4-methylumbelliferone moiety of AF40431 forming π-stacking with a phenylalanine.

scholarly journals Evidence vs Expectations: How to validate your ligand in a protein structure

2014 ◽  
Vol 70 (a1) ◽  
pp. C1479-C1479
Author(s):  
Edwin Pozharski
Keyword(s):  
Structural Biology ◽  
Complex Structure ◽  
Structural Data ◽  
High Expectation ◽  
Ligand Complex ◽  
Ligand Interaction ◽  
Protein Ligand Interaction ◽  
Experimental Findings ◽  
Small Molecule Ligand

Determination of a protein-ligand complex structure is essential in many areas of structural biology. Details of the interactions between protein and a small molecule ligand often represent major findings from a crystal structure. Thorough validation of interpretation of such structural data is particularly important given high expectation of confirming prior experimental findings regarding targeted protein-ligand interaction. Modern methods of ligand validation are discussed and illustrated.

Single Crystal Growth of High-Pressure Phases of Ice and Salt Hydrate Far Below the Original Melting Point by Mixing Alcohol: Crystal Structure Determination of Magnesium Chloride Heptahydrate

2020 ◽  
Author(s):  
Keishiro Yamashita ◽  
Kazuki Komatsu ◽  
Hiroyuki Kagi
Keyword(s):  
Crystal Structure ◽  
High Pressure ◽  
Crystal Growth ◽  
Single Crystal ◽  
Room Temperature ◽  
Growth Technique ◽  
Salt Hydrate ◽  
X Ray

An crystal-growth technique for single crystal x-ray structure analysis of high-pressure forms of hydrogen-bonded crystals is proposed. We used alcohol mixture (methanol: ethanol = 4:1 in volumetric ratio), which is a widely used pressure transmitting medium, inhibiting the nucleation and growth of unwanted crystals. In this paper, two kinds of single crystals which have not been obtained using a conventional experimental technique were obtained using this technique: ice VI at 1.99 GPa and MgCl<sub>2</sub>·7H<sub>2</sub>O at 2.50 GPa at room temperature. Here we first report the crystal structure of MgCl2·7H2O. This technique simultaneously meets the requirement of hydrostaticity for high-pressure experiments and has feasibility for further in-situ measurements.

Refinement of the crystal structure of sieleckiite and revision of its symmetry

2017 ◽  
Vol 81 (4) ◽  
pp. 917-922
Author(s):  
Peter Elliott
Keyword(s):  
Crystal Structure ◽  
Synchrotron Radiation ◽  
Single Crystal ◽  
Diffraction Data ◽  
X Ray Diffraction ◽  
Aluminium Phosphate ◽  
Unit Cell Parameters ◽  
X Ray ◽  
Cell Parameters ◽  
Phosphate Mineral

AbstractThe crystal structure of the copper aluminium phosphate mineral sieleckiite, Cu3Al4(PO4)2 (OH)12·2H2O, from the Mt Oxide copper mine, Queensland, Australia was solved from single-crystal X-ray diffraction data utilizing synchrotron radiation. Sieleckiite has monoclinic rather than triclinic symmetry as previously reported and is space group C2/m with unit-cell parameters a = 11.711(2), b = 6.9233(14), c = 9.828(2) Å, β = 92.88(3)°, V = 795.8(3) Å3and Z = 2. The crystal structure, which has been refined to R1 = 0.0456 on the basis of 1186 unique reflections with Fo > 4σF, is a framework of corner-, edge- and face- sharing Cu and Al octahedra and PO4 tetrahedra.

X‐ray determination of the Debye temperature at high pressure using high‐energy synchrotron radiation

1990 ◽  
Vol 68 (6) ◽  
pp. 2719-2722 ◽  
Author(s):  
A. Matsumuro ◽  
M. Kobayashi ◽  
T. Kikegawa ◽  
M. Senoo
Keyword(s):  
High Pressure ◽  
Synchrotron Radiation ◽  
Debye Temperature ◽  
High Energy ◽  
X Ray

Structure determination of the 1/1 α/β mixed lactose by X-ray powder diffraction

2005 ◽  
Vol 61 (4) ◽  
pp. 455-463 ◽  
Author(s):  
Jacques Lefebvre ◽  
Jean-François Willart ◽  
Vincent Caron ◽  
Ronan Lefort ◽  
Frédéric Affouard ◽  
...  
Keyword(s):  
Powder Diffraction ◽  
Size Effects ◽  
Room Temperature ◽  
Real Space ◽  
Hydroxyl Groups ◽  
Soft Constraints ◽  
Rietveld Refinements ◽  
X Ray ◽  
Mixed Compound

The mixed form of α/β lactose was obtained by heating amorphous α-lactose at 443 K. NMR spectroscopy determined the stoichiometry of this mixed compound to be 1/1. The X-ray powder diffraction pattern was recorded at room temperature with a sensitive curved detector (CPS 120). The structure was solved by real-space methods (simulated annealing) followed by Rietveld refinements with soft constraints on bond lengths and bond angles. The H atoms of the hydroxyl groups were localized by minimization of the crystalline energy. The cell of 1/1 α/β lactose is triclinic with the space group P1 and contains two molecules (one molecule of each anomer). The crystalline cohesion is achieved by networks of O—H...O hydrogen bonds. The width of the Bragg peaks is interpreted through a microstructural approach in terms of isotropic strain effects and anisotropic size effects.

Determination of the alloying content in the matrix of Zr alloys using synchrotron radiation microprobe X-ray fluorescence

2003 ◽  
Vol 321 (2-3) ◽  
pp. 221-232 ◽  
Author(s):  
A Yilmazbayhan ◽  
O Delaire ◽  
A.T Motta ◽  
R.C Birtcher ◽  
J.M Maser ◽  
...  
Keyword(s):  
Synchrotron Radiation ◽  
X Ray ◽  
The Matrix ◽  
Zr Alloys

Recent insights into lytic polysaccharide monooxygenases (LPMOs)

2018 ◽  
Vol 46 (6) ◽  
pp. 1431-1447 ◽  
Author(s):  
Tobias Tandrup ◽  
Kristian E. H. Frandsen ◽  
Katja S. Johansen ◽  
Jean-Guy Berrin ◽  
Leila Lo Leggio
Keyword(s):  
Active Site ◽  
Room Temperature ◽  
Experimental Studies ◽  
Binding Mode ◽  
Structural Features ◽  
Oxygen Species ◽  
Animal Kingdom ◽  
X Ray ◽  
Lytic Polysaccharide Monooxygenases ◽  
Polysaccharide Monooxygenases

Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes discovered within the last 10 years. By degrading recalcitrant substrates oxidatively, these enzymes are major contributors to the recycling of carbon in nature and are being used in the biorefinery industry. Recently, two new families of LPMOs have been defined and structurally characterized, AA14 and AA15, sharing many of previously found structural features. However, unlike most LPMOs to date, AA14 degrades xylan in the context of complex substrates, while AA15 is particularly interesting because they expand the presence of LPMOs from the predominantly microbial to the animal kingdom. The first two neutron crystallography structures have been determined, which, together with high-resolution room temperature X-ray structures, have putatively identified oxygen species at or near the active site of LPMOs. Many recent computational and experimental studies have also investigated the mechanism of action and substrate-binding mode of LPMOs. Perhaps, the most significant recent advance is the increasing structural and biochemical evidence, suggesting that LPMOs follow different mechanistic pathways with different substrates, co-substrates and reductants, by behaving as monooxygenases or peroxygenases with molecular oxygen or hydrogen peroxide as a co-substrate, respectively.

Structure Determination of 3,5-Biscyclohexylidene-1,2,4-trithiolane / Structure Determination of 3,5-Biscyclohexylidene-1,2,4-trithiolane

1980 ◽  
Vol 35 (8) ◽  
pp. 1015-1018 ◽  
Author(s):  
Werner Winter ◽  
Hanspeter Bühl ◽  
Herbert Meier
Keyword(s):  
General Formula ◽  
Structure Determination ◽  
Title Compound ◽  
Direct Methods ◽  
Spectroscopic Techniques ◽  
Space Group ◽  
X Ray ◽  
Cell Parameters ◽  
Final Structure

Abstract Fragmentation of 1,2,3-thiadiazoles (1) leads to the compounds 5 - 8 with an increasing proportion of sulphur. Numerous structural possibilities exist for the products 7 with the general formula (R2C2)2S3. The number of proposals can be reduced by spectroscopic techniques, but the final structure determination is accomplished by an X-ray analysis of the title compound 7a. 7a crystallizes in the space group P21/c (Z = 4) with cell parameters of a = 9.714(1), b = 16.188(8), c = 9.149(2) Å and β = 98.93(1)°. The structure is solved by direct methods and refined to R = 0.053 with 1955 diffractometer data (I ≥ 2σ(I)). The trithiolane ring has a puckered conformation and the whole molecule shows nearly perfect C2-symmetry, which is not required crystallographically.

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