Crystal structure of Npun_R1517, a putative negative regulator of heterocyst differentiation fromNostoc punctiformePCC 73102

STIP1 homology and U-Box containing protein 1 (STUB1) plays a key role in maintaining cell health during stress and aging. Recent evidence suggested STUB1 also helps regulate immunity with the potential of clearing malignant cells. Indeed, we and others have shown that STUB1 is a pivotal negative regulator of interferon gamma sensing – a process critical to the immunosurveillance of tumors and pathogens. Thus far, investigation of STUB1’s role relies mostly on genetic approaches as pharmacological inhibitors of this protein are lacking. Identification of a STUB1 tool compound is important as it would allow therapeutically relevant target validation in a broader sense. Accordingly, we leveraged phage display and computational modeling to identify and refine STUB1 binders. Screening of >10E9 macrocyclic peptides resulted in several conserved motifs as well as structurally diverse leads. Co-crystal structure of the peptide hit and STUB1 has enabled us to employ structure-based in silico design for further optimization. Of the modifications employed, replacing the hydrophilic solvent-exposed region of the macrocyclic peptides with a hydrophobic scaffold improved cellular permeability, while the binding conformation was maintained. Further substitution of the permeability-limiting terminal aspartic acid with a tetrazole bioisostere retained the binding to certain extent while improving permeability, suggesting a path forward. The current lead, although not optimal for cellular study, provides a valuable template for further development into selective tool compounds for STUB1 to enable target validation.

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Crystal structure of PhoU from Pseudomonas aeruginosa, a negative regulator of the Pho regulon

Journal of Structural Biology ◽

10.1016/j.jsb.2014.08.010 ◽

2014 ◽

Vol 188 (1) ◽

pp. 22-29 ◽

Cited By ~ 5

Author(s):

Sang Jae Lee ◽

Ye Seol Park ◽

Soon-Jong Kim ◽

Bong-Jin Lee ◽

Se Won Suh

Keyword(s):

Crystal Structure ◽

Pseudomonas Aeruginosa ◽

Negative Regulator ◽

Pho Regulon

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Crystal Structure Determination of Glycerol-Containing Lipids from Electron Diffraction Data. Use of Analog Compounds Based upon Configurational Isomers of Cyclopentane-1, 2, 3-TRIOL

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077761 ◽

1977 ◽

Vol 35 ◽

pp. 24-25

Author(s):

Douglas L. Dorset ◽

Anthony J. Hancock

Keyword(s):

Crystal Structure ◽

Electron Diffraction ◽

Diffraction Data ◽

Structure Determination ◽

Crystal Surface ◽

Coherent Scattering ◽

Crystal Structure Determination ◽

Electron Diffraction Data ◽

Polar Group ◽

Axis Orientation

Lipids containing long polymethylene chains were among the first compounds subjected to electron diffraction structure analysis. It was only recently realized, however, that various distortions of thin lipid microcrystal plates, e.g. bends, polar group and methyl end plane disorders, etc. (1-3), restrict coherent scattering to the methylene subcell alone, particularly if undistorted molecular layers have well-defined end planes. Thus, ab initio crystal structure determination on a given single uncharacterized natural lipid using electron diffraction data can only hope to identify the subcell packing and the chain axis orientation with respect to the crystal surface. In lipids based on glycerol, for example, conformations of long chains and polar groups about the C-C bonds of this moiety still would remain unknown.One possible means of surmounting this difficulty is to investigate structural analogs of the material of interest in conjunction with the natural compound itself. Suitable analogs to the glycerol lipids are compounds based on the three configurational isomers of cyclopentane-1,2,3-triol shown in Fig. 1, in which three rotameric forms of the natural glycerol derivatives are fixed by the ring structure (4-7).

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Spherulitic crystal growth in the prodissoconch larval of Crassostrea virginica

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100076263 ◽

1983 ◽

Vol 41 ◽

pp. 518-519

Author(s):

George G. Cocks ◽

Louis Leibovitz ◽

DoSuk D. Lee

Keyword(s):

Crystal Structure ◽

Crassostrea Virginica ◽

Crystal Orientation ◽

Developmental Changes ◽

Gastrula Stage ◽

Orthorhombic Crystal ◽

Orthorhombic Crystal Structure ◽

Stages Of Growth ◽

Early Stages ◽

Initial Deposition

Our understanding of the structure and the formation of inorganic minerals in the bivalve shells has been considerably advanced by the use of electron microscope. However, very little is known about the ultrastructure of valves in the larval stage of the oysters. The present study examines the developmental changes which occur between the time of conception to the early stages of Dissoconch in the Crassostrea virginica(Gmelin), focusing on the initial deposition of inorganic crystals by the oysters.The spawning was induced by elevating the temperature of the seawater where the adult oysters were conditioned. The eggs and sperm were collected separately, then immediately mixed for the fertilizations to occur. Fertilized animals were kept in the incubator where various stages of development were stopped and observed. The detailed analysis of the early stages of growth showed that CaCO3 crystals(aragonite), with orthorhombic crystal structure, are deposited as early as gastrula stage(Figuresla-b). The next stage in development, the prodissoconch, revealed that the crystal orientation is in the form of spherulites.

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Transmission Electron Microscopy studies of the vacancy ordering in YSI2-X thin films

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100087124 ◽

1991 ◽

Vol 49 ◽

pp. 562-563

Author(s):

F.-R. Chen ◽

T. L. Lee ◽

L. J. Chen

Keyword(s):

Crystal Structure ◽

Electron Microscopy ◽

Thin Films ◽

Diffraction Pattern ◽

Annealing Temperature ◽

Lattice Mismatch ◽

Si Substrate ◽

Metal Thin Films ◽

Transmission Electron ◽

Vacancy Ordering

YSi2-x thin films were grown by depositing the yttrium metal thin films on (111)Si substrate followed by a rapid thermal annealing (RTA) at 450 to 1100°C. The x value of the YSi2-x films ranges from 0 to 0.3. The (0001) plane of the YSi2-x films have an ideal zero lattice mismatch relative to (111)Si surface lattice. The YSi2 has the hexagonal AlB2 crystal structure. The orientation relationship with Si was determined from the diffraction pattern shown in figure 1(a) to be and . The diffraction pattern in figure 1(a) was taken from a specimen annealed at 500°C for 15 second. As the annealing temperature was increased to 600°C, superlattice diffraction spots appear at position as seen in figure 1(b) which may be due to vacancy ordering in the YSi2-x films. The ordered vacancies in YSi2-x form a mesh in Si plane suggested by a LEED experiment.

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Crystal Structure Analysis of Cu-Zr Alloys by Convergent Beam Diffraction

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100098277 ◽

1981 ◽

Vol 39 ◽

pp. 354-355

Author(s):

A. F. Marshall ◽

J. W. Steeds ◽

D. Bouchet ◽

S. L. Shinde ◽

R. G. Walmsley

Keyword(s):

Crystal Structure ◽

Point Group ◽

Intermetallic Phase ◽

Three Dimensional ◽

Crystal Structure Analysis ◽

Ion Milling ◽

Composition And Structure ◽

Unit Cells ◽

Sputter Deposited ◽

Convergent Beam

Convergent beam electron diffraction is a powerful technique for determining the crystal structure of a material in TEM. In this paper we have applied it to the study of the intermetallic phases in the Cu-rich end of the Cu-Zr system. These phases are highly ordered. Their composition and structure has been previously studied by microprobe and x-ray diffraction with sometimes conflicting results.The crystalline phases were obtained by annealing amorphous sputter-deposited Cu-Zr. Specimens were thinned for TEM by ion milling and observed in a Philips EM 400. Due to the large unit cells involved, a small convergence angle of diffraction was used; however, the three-dimensional lattice and symmetry information of convergent beam microdiffraction patterns is still present. The results are as follows:1) 21 at% Zr in Cu: annealed at 500°C for 5 hours. An intermetallic phase, Cu3.6Zr (21.7% Zr), space group P6/m has been proposed near this composition (2). The major phase of our annealed material was hexagonal with a point group determined as 6/m.

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