Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone activates gene transcription of the serine protease inhibitors (SPI) 2.1 and 2.2 by an unknown mechanism. In order to define the promoter regions responsible for this effect and to characterize the transcription factors involved, we have performed gel electrophoresis mobility shift assays on nuclear extracts from cell lines transfected with growth hormone receptor cDNA. We have identified a 9-base pair DNA element, the SPI-GLE 1, which forms a complex with nuclear proteins following activation by growth hormone and which, when placed upstream of a minimal thymidine kinase promoter, drives chloramphenicol acetyltransferase expression in a growth hormone-dependent fashion. This element is similar to those from several genes regulated by other cytokines including interferon. The growth hormone-induced complexes formed were dependent on tyrosine phosphorylation but did not contain the interferon-gamma-activated transcription factor Stat 91. Competition studies with oligonucleotides similar to the SPI-GLE 1 reveal the sequence of a consensus element that specifically binds growth hormone-regulated nuclear proteins.
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PMID:Growth hormone specifically regulates serine protease inhibitor gene transcription via gamma-activated sequence-like DNA elements. 792 35

An attempt toward screening of phytoconstituents (Arisaema genus) against herpes viruses (HSV-1 and HSV-2) was carried out using in silico approaches. Human HSV-1 and HSV-2 are accountable for cold sores genital herpes, respectively. Two drug targets, namely thymidine kinase (TK; PDB: 2ki5) serine protease (PDB: 1at3) were selected for HSV-1 and HSV-2. Initially, molecular docking tool was employed to screened apex hits phytoconstituents against herpes infections. ADME-T studies of top ranked were also further highlighted to achieve their effectiveness. Following, molecular dynamics studies were also examined to further optimize the stability of ligands. Glide scores and binding interactions of phytoconstituents were compared with Acyclovir, the main drug used in treatment of HSV, the screened top hits exhibited more glide scores and better binding for both HSV-1 and HSV-2 receptors. Additionally, ADME-T showed an ideal range for top hits while molecular dynamics results also illustrated stability of models. Ultimately, the whole efforts reveal to top three most promising hits for HSV-1 (39, 21, 19) and HSV-2 (20, 51, 19) receptors which can be explored further in wet lab experiments as promising agents against HSV infections.
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PMID:A merged molecular docking, ADME-T and dynamics approaches towards the genus of Arisaema as herpes simplex virus type 1 and type 2 inhibitors. 3057 34