scholarly journals Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria parasites

2021 ◽  
Author(s):  
Philip M Frasse ◽  
Justin J Miller ◽  
Ebrahim Soleimani ◽  
Jian-She Zhu ◽  
David L Jakeman ◽  
...  
Keyword(s):  
Malaria Parasite ◽  
Three Dimensional ◽  
Complex Life Cycle ◽  
Parasite Development ◽  
Gpi Anchor ◽  
Multi Stage ◽  
Transgenic Parasites ◽  
Parasite Egress ◽  
Dimensional Crystal

The malaria parasite Plasmodium falciparum is responsible for over 200 million infections and 400,000 deaths per year. At multiple stages during its complex life cycle, P. falciparum expresses several essential proteins tethered to its surface by glycosylphosphatidylinositol (GPI) anchors, which are critical for biological processes such as parasite egress and reinvasion of host red blood cells. Targeting this pathway therapeutically has the potential to broadly impact parasite development across several life stages. Here, we characterize an upstream component of GPI anchor biosynthesis, the putative phosphomannomutase (EC 5.4.2.8) of the parasites, HAD5 (PF3D7_1017400). We confirm the phosphomannomutase and phosphoglucomutase activity of purified recombinant HAD5. By regulating expression of HAD5 in transgenic parasites, we demonstrate that HAD5 is required for malaria parasite egress and erythrocyte reinvasion. Finally, we determine the three-dimensional crystal structure of HAD5 and identify a substrate analog that specifically inhibits HAD5, compared to orthologous human phosphomannomutases. These findings demonstrate that the GPI anchor biosynthesis pathway is exceptionally sensitive to inhibition, and that HAD5 has potential as a multi-stage antimalarial target.

Synthesis, crystal structure and characterization of a three-dimensional CdII coordination polymer constructed from 2,5-bis(1H-1,2,4-triazol-1-yl)terephthalate

2018 ◽  
Vol 74 (2) ◽  
pp. 166-170 ◽  
Author(s):  
Li Meng ◽  
Miao-Li Zhu ◽  
Li-Ping Lu
Keyword(s):  
Crystal Structure ◽  
Coordination Polymer ◽  
Three Dimensional ◽  
X Ray ◽  
Distorted Octahedral ◽  
Ft Ir ◽  
A Chain ◽  
Coordinated Water ◽  
Dimensional Crystal

Bifunctional organic ligands are very popular for the design of coordination polymers because they allow the formation of a great diversity of structures. In the title coordination polymer, the new bifunctional inversion-symmetric ligand 2,5-bis(1H-1,2,4-triazol-1-yl)terephthalic acid (abbreviated as H2bttpa) links CdII cations, giving rise to the three-dimensional CdII coordination polymer catena-poly[diaqua[μ4-2,5-bis(1H-1,2,4-triazol-1-yl)terephthalato-κ4 O 1:O 4:N 4:N 4′]cadmium(II)], [Cd(C12H6N6O4)(H2O)2] n or [Cd(bttpa)(H2O)2] n . The asymmetric unit consists of half a CdII cation, half a bttpa2− ligand and one coordinated water molecule. The CdII cation is located on a twofold axis and is hexacoordinated in a distorted octahedral environment of four O and two N atoms. Four different bttpa2− ligands contribute to this coordination, with two carboxylate O atoms in trans positions and two triazole N atoms in cis positions. Two aqua ligands in cis positions complete the coordination sphere. The fully deprotonated bttpa2− ligand sits about a crystallographic centre of inversion and links two CdII cations to form a chain in a μ2-terephthalato-κ2 O 1:O 4 bridge. This chain extends in the other two directions via the triazole heterocycles, producing a three-dimensional framework. O—H...O hydrogen bonds and weak C—H...N interactions stabilize the three-dimensional crystal structure. The FT–IR spectrum, X-ray powder pattern, thermogravimetric behaviour and solid-state photoluminescence of the title polymer have been investigated. The photoluminescence is enhanced and red-shifted with respect to the uncoordinated ligand.

scholarly journals Gene regulation of the avian malaria parasite Plasmodium relictum, during the different stages within the mosquito vector

2020 ◽  
Author(s):  
V. Sekar ◽  
A. Rivero ◽  
R. Pigeault ◽  
S. Gandon ◽  
A. Drews ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Malaria Parasite ◽  
Avian Malaria ◽  
Phase Iii ◽  
Complex Life Cycle ◽  
Parasite Development ◽  
Plasmodium Relictum ◽  
Natural Vector ◽  
Avian Malaria Parasite

AbstractThe malaria parasite Plasmodium relictum is one of the most widespread species of avian malaria. As is the case in its human counterparts, bird Plasmodium undergoes a complex life cycle infecting two hosts: the arthropod vector and the vertebrate host. In this study, we examine the transcriptome of P. relictum (SGS1) during crucial timepoints within its natural vector, Culex pipiens quinquefasciatus. Differential gene-expression analyses identified genes linked to the parasites life-stages at: i) a few minutes after the blood meal is ingested, ii) during peak oocyst production phase, iii) during peak sporozoite phase and iv) during the late-stages of the infection. A large amount of genes coding for functions linked to host-immune invasion and multifunctional genes was active throughout the infection cycle. One gene associated with a conserved Plasmodium membrane protein with unknown function was upregulated throughout the parasite development in the vector, suggesting an important role in the successful completion of the sporogonic cycle. Transcript annotation further revealed novel genes, which were significantly differentially expressed during the infection in the vector as well as upregulation of reticulocyte-binding proteins, which raises the possibility of the multifunctionality of these RBPs. We establish the existence of highly stage-specific pathways being overexpressed during the infection. This first study of gene-expression of a non-human Plasmodium species in its natural vector provides a comprehensive insight into the molecular mechanisms of the common avian malaria parasite P. relictum and provides essential information on the evolutionary diversity in gene regulation of the Plasmodium’s vector stages.

scholarly journals Malaria parasite egress at a glance

2021 ◽  
Vol 134 (5) ◽  
pp. jcs257345
Author(s):  
Michele S. Y Tan ◽  
Michael J. Blackman
Keyword(s):  
Life Cycle ◽  
Malaria Control ◽  
Cyst Wall ◽  
Malaria Parasite ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Complex Life Cycle ◽  
Intracellular Pathogens ◽  
Parasite Egress ◽  
Intracellular Vacuole

ABSTRACTAll intracellular pathogens must escape (egress) from the confines of their host cell to disseminate and proliferate. The malaria parasite only replicates in an intracellular vacuole or in a cyst, and must undergo egress at four distinct phases during its complex life cycle, each time disrupting, in a highly regulated manner, the membranes or cyst wall that entrap the parasites. This Cell Science at a Glance article and accompanying poster summarises our current knowledge of the morphological features of egress across the Plasmodium life cycle, the molecular mechanisms that govern the process, and how researchers are working to exploit this knowledge to develop much-needed new approaches to malaria control.

Three-dimensional Crystal Structure and Enzymic Characterization of β-Mannanase Man5A from Blue Mussel Mytilus edulis

2006 ◽  
Vol 357 (5) ◽  
pp. 1500-1510 ◽  
Author(s):  
Anna M. Larsson ◽  
Lars Anderson ◽  
Bingze Xu ◽  
Inés G. Muñoz ◽  
Isabel Usón ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mytilus Edulis ◽  
Blue Mussel ◽  
Three Dimensional ◽  
Dimensional Crystal

scholarly journals Synthesis and Characterization of (Z)-Furan-2-carbaldehyde Thiosemicarbazone at Low Temperature

2010 ◽  
Vol 7 (s1) ◽  
pp. S294-S298 ◽  
Author(s):  
Alireza Abbasi ◽  
Shokoofeh Geranmayeh ◽  
Ali Naghi Taheri ◽  
Hashem Shahroosvand ◽  
Mohsen Shabani
Keyword(s):  
Crystal Structure ◽  
Three Dimensional ◽  
Synthesis And Characterization ◽  
Monoclinic Space Group ◽  
X Ray ◽  
Π Interactions ◽  
Compound C ◽  
Weak Hydrogen Bonds ◽  
Dimensional Crystal

The compound, C6H7N3OS, has been prepared and characterized by condensation between thiosemicarbazide and furan-2-carbaldehyde and its structure was elucidated by x-ray analysis (at 150 K), NMR and IR spectroscopy methods (at ambient temperature). It crystallizes in the monoclinic space groupP21/c(No. 14), a = 13.5099(3) Å, b = 5.67430(10) Å, c = 23.4755(6) Å, β= 117.367(2)°, V = 1598.20(7) Å3and Z = 8. The crystal structure was solved and refined to R = 0.0290 with 2942 unique reflections. No significant π-π interactions are found in the crystal structure. There are C-H…π interactions and also different weak hydrogen bonds, stabilizing the three dimensional crystal structure.

Characterization of photosystem II with the atomic-force microscope

1992 ◽  
Vol 50 (2) ◽  
pp. 1146-1147
Author(s):  
Kathleen M. Marr ◽  
Mary K. Lyon
Keyword(s):  
Photosystem Ii ◽  
Atomic Force Microscope ◽  
Three Dimensional ◽  
Biologically Active ◽  
Atomic Force ◽  
Freeze Etching ◽  
Image Averaging ◽  
Oxygen Evolving ◽  
Averaging Techniques

Photosystem II (PSII) is different from all other reaction centers in that it splits water to evolve oxygen and hydrogen ions. This unique ability to evolve oxygen is partly due to three oxygen evolving polypeptides (OEPs) associated with the PSII complex. Freeze etching on grana derived insideout membranes revealed that the OEPs contribute to the observed tetrameric nature of the PSIl particle; when the OEPs are removed, a distinct dimer emerges. Thus, the surface of the PSII complex changes dramatically upon removal of these polypeptides. The atomic force microscope (AFM) is ideal for examining surface topography. The instrument provides a topographical view of individual PSII complexes, giving relatively high resolution three-dimensional information without image averaging techniques. In addition, the use of a fluid cell allows a biologically active sample to be maintained under fully hydrated and physiologically buffered conditions. The OEPs associated with PSII may be sequentially removed, thereby changing the surface of the complex by one polypeptide at a time.

convergent-beam diffraction from surfaces

1987 ◽  
Vol 45 ◽  
pp. 30-33
Author(s):  
J. A. Eades ◽  
A. E. Smith ◽  
D. F. Lynch
Keyword(s):  
Reciprocal Lattice ◽  
Three Dimensional ◽  
Grazing Incidence ◽  
Three Dimensions ◽  
Plane Figure ◽  
Transmission Electron ◽  
Convergent Beam ◽  
Beam Patterns ◽  
Beam Diffraction

It is quite simple (in the transmission electron microscope) to obtain convergent-beam patterns from the surface of a bulk crystal. The beam is focussed onto the surface at near grazing incidence (figure 1) and if the surface is flat the appropriate pattern is obtained in the diffraction plane (figure 2). Such patterns are potentially valuable for the characterization of surfaces just as normal convergent-beam patterns are valuable for the characterization of crystals.There are, however, several important ways in which reflection diffraction from surfaces differs from the more familiar electron diffraction in transmission.GeometryIn reflection diffraction, because of the surface, it is not possible to describe the specimen as periodic in three dimensions, nor is it possible to associate diffraction with a conventional three-dimensional reciprocal lattice.

Construction of plastic contact deformation maps on ceramics: a case study on aluminum nitride

1996 ◽  
Vol 54 ◽  
pp. 636-637
Author(s):  
D. L. Callahan
Keyword(s):  
Plastic Deformation ◽  
Aluminum Nitride ◽  
Mechanical Response ◽  
Three Dimensional ◽  
Bright Field Image ◽  
Perfectly Plastic ◽  
Contrast Analysis ◽  
Deformation Patterns

Modern polishing, precision machining and microindentation techniques allow the processing and mechanical characterization of ceramics at nanometric scales and within entirely plastic deformation regimes. The mechanical response of most ceramics to such highly constrained contact is not predictable from macroscopic properties and the microstructural deformation patterns have proven difficult to characterize by the application of any individual technique. In this study, TEM techniques of contrast analysis and CBED are combined with stereographic analysis to construct a three-dimensional microstructure deformation map of the surface of a perfectly plastic microindentation on macroscopically brittle aluminum nitride.The bright field image in Figure 1 shows a lg Vickers microindentation contained within a single AlN grain far from any boundaries. High densities of dislocations are evident, particularly near facet edges but are not individually resolvable. The prominent bend contours also indicate the severity of plastic deformation. Figure 2 is a selected area diffraction pattern covering the entire indentation area.

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