11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Development by Lentiviral Screening Based on Computational Modeling

Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 169-179
Author(s):  
Haifeng Liu ◽  
Lingyu Li ◽  
Chunlei Zhang ◽  
Hongzhi Li ◽  
Jieting Liu ◽  
...  
Keyword(s):  
Viral Vector ◽  
Three Dimensional ◽  
Hydroxysteroid Dehydrogenase ◽  
Gene Bank ◽  
Dimensional Structure ◽  
Drug Candidate ◽  
Lentiviral Transduction ◽  
Stable Manner

In this study, rat and human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have been cloned by lentiviral transduction and expressed by CHO-K1 cells. The results showed that recombinant plasmids contained R11bhsd1 or H11bhsd1 have been constructed, which is consistent with the gene bank respectively. A clone cell was selected with G418 and cultivated to express 11β-HSD1. 11β-HSD1 catalytic activity of rat and human were 99.5 and 98.7%, respectively, determined by scanning radiometer. And the cloned CHO-K1 cells expressed the protein of 11β-HSD1 in a long-term and stable manner, which makes it suitable for screening 11β-HSD1 inhibitor. The three-dimensional structure of 11β-HSD1 was used for studying the interaction between inhibitor and enzyme by the binding poses predicted by AutoDock and LeDock software. The docking results revealed that compound 8 forms 2 hydrogen bonds with the residues of Gly-216 and Ile-218 in 11β-HSD1, that is to say compound 8 maybe a good 11β-HSD1 inhibitor. Moreover, C57BL/6 mice with R11bHsd1 overexpression had a higher body weight, glucose, total cholesterol, and triglyceride levels compared to the mice treated with an empty viral vector. The results might provide a beneficial foundation for selecting inhibitors of 11β-HSD1 or for researching drug candidate mechanisms.

scholarly journals High-resolution three-dimensional probes of biomaterials and their interfaces

2012 ◽  
Vol 370 (1963) ◽  
pp. 1337-1351 ◽  
Author(s):  
Kathryn Grandfield ◽  
Anders Palmquist ◽  
Håkan Engqvist
Keyword(s):  
High Resolution ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Controlled Drug Release ◽  
Biological Tissues ◽  
Dimensional Structure ◽  
Bone Interface ◽  
Biomaterial Interfaces ◽  
Titania Coating

Interfacial relationships between biomaterials and tissues strongly influence the success of implant materials and their long-term functionality. Owing to the inhomogeneity of biological tissues at an interface, in particular bone tissue, two-dimensional images often lack detail on the interfacial morphological complexity. Furthermore, the increasing use of nanotechnology in the design and production of biomaterials demands characterization techniques on a similar length scale. Electron tomography (ET) can meet these challenges by enabling high-resolution three-dimensional imaging of biomaterial interfaces. In this article, we review the fundamentals of ET and highlight its recent applications in probing the three-dimensional structure of bioceramics and their interfaces, with particular focus on the hydroxyapatite–bone interface, titanium dioxide–bone interface and a mesoporous titania coating for controlled drug release.

Hepatocyte Aggregate Culture Technique for Bioreactors in Hybrid Liver Support Systems

1993 ◽  
Vol 16 (12) ◽  
pp. 843-846 ◽  
Author(s):  
J.C. Gerlach ◽  
K. Klöppel ◽  
C. MÜller ◽  
N. Schnoy ◽  
M.D. Smith ◽  
...  
Keyword(s):  
High Performance ◽  
Large Scale ◽  
Support Systems ◽  
Three Dimensional ◽  
Culture Technique ◽  
Dimensional Structure ◽  
Cell Aggregates ◽  
Liver Support ◽  
Aggregate Culture

Utilizing a modified culture technique for hepatocytes, a high performance suspension culture is possible in which hepatocytes spontaneously form cell aggregates. The aggregates of 20-100 cells have been histologically confirmed to hold a three-dimensional structure, they show a long-term external metabolism and a survival time comparable with standard adhesion cultures. This technique has several advantages in the construction of large scale bioreactors for hybrid liver support systems.

scholarly journals Three-dimensional structure of a mouse-adapted type 2/type 1 poliovirus chimera.

1991 ◽  
Vol 10 (9) ◽  
pp. 2331-2341 ◽  
Author(s):  
T.O. Yeates ◽  
D.H. Jacobson ◽  
A. Martin ◽  
C. Wychowski ◽  
M. Girard ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure

Three-dimensional Structure of the Human Immunodeficiency Virus Type 1 Matrix Protein

1994 ◽  
Vol 244 (2) ◽  
pp. 198-223 ◽  
Author(s):  
Michael A. Massiah ◽  
Mary R. Starich ◽  
Chiana Paschall ◽  
Michael F. Summers ◽  
Allyson M. Christensen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Matrix Protein ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Immunodeficiency Virus

scholarly journals Cloning, Baeyer-Villiger Biooxidations, and Structures of the Camphor Pathway 2-Oxo-Δ3-4,5,5-Trimethylcyclopentenylacetyl-Coenzyme A Monooxygenase of Pseudomonas putida ATCC 17453

2012 ◽  
Vol 78 (7) ◽  
pp. 2200-2212 ◽  
Author(s):  
Hannes Leisch ◽  
Rong Shi ◽  
Stephan Grosse ◽  
Krista Morley ◽  
Hélène Bergeron ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Pseudomonas Putida ◽  
Coenzyme A ◽  
Free Acid ◽  
Three Dimensional ◽  
Catalytic Efficiency ◽  
Dimensional Structure ◽  
Content Type ◽  
Crystal Forms

ABSTRACTA dimeric Baeyer-Villiger monooxygenase (BVMO) catalyzing the lactonization of 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-coenzyme A (CoA), a key intermediate in the metabolism of camphor byPseudomonas putidaATCC 17453, had been initially characterized in 1983 by Ougham and coworkers (H. J. Ougham, D. G. Taylor, and P. W. Trudgill, J. Bacteriol. 153:140–152, 1983). Here we cloned and overexpressed the 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase (OTEMO) inEscherichia coliand determined its three-dimensional structure with bound flavin adenine dinucleotide (FAD) at a 1.95-Å resolution as well as with bound FAD and NADP+at a 2.0-Å resolution. OTEMO represents the first homodimeric type 1 BVMO structure bound to FAD/NADP+. A comparison of several crystal forms of OTEMO bound to FAD and NADP+revealed a conformational plasticity of several loop regions, some of which have been implicated in contributing to the substrate specificity profile of structurally related BVMOs. Substrate specificity studies confirmed that the 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetic acid coenzyme A ester is preferred over the free acid. However, the catalytic efficiency (kcat/Km) favors 2-n-hexyl cyclopentanone (4.3 × 105M−1s−1) as a substrate, although its affinity (Km= 32 μM) was lower than that of the CoA-activated substrate (Km= 18 μM). In whole-cell biotransformation experiments, OTEMO showed a unique enantiocomplementarity to the action of the prototypical cyclohexanone monooxygenase (CHMO) and appeared to be particularly useful for the oxidation of 4-substituted cyclohexanones. Overall, this work extends our understanding of the molecular structure and mechanistic complexity of the type 1 family of BVMOs and expands the catalytic repertoire of one of its original members.

scholarly journals Visualization of Tegument-Capsid Interactions and DNA in Intact Herpes Simplex Virus Type 1 Virions

1999 ◽  
Vol 73 (4) ◽  
pp. 3210-3218 ◽  
Author(s):  
Z. Hong Zhou ◽  
Dong Hua Chen ◽  
Joanita Jakana ◽  
Frazer J. Rixon ◽  
Wah Chiu
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Cellular Transport ◽  
Capsid Shell ◽  
Simplex Virus

ABSTRACT Herpes simplex virus type 1 virions were examined by electron cryomicroscopy, allowing the three-dimensional structure of the infectious particle to be visualized for the first time. The capsid shell is identical to that of B-capsids purified from the host cell nucleus, with the exception of the penton channel, which is closed. The double-stranded DNA genome is organized as regularly spaced (∼26 Å) concentric layers inside the capsid. This pattern suggests a spool model for DNA packaging, similar to that for some bacteriophages. The bulk of the tegument is not icosahedrally ordered. However, a small portion appears as filamentous structures around the pentons, interacting extensively with the capsid. Their locations and interactions suggest possible roles for the tegument proteins in regulating DNA transport through the penton channel and binding to cellular transport proteins during viral infection.

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