Thus, chemical array will offer a powerful platform to identify new drug candidates against infectious diseases. Further in-depth studies including derivative analysis and in vivo infection experiments are expected to present a new class of anti-HBV agents. Entecavir was purchased from Santa Cruz Biotechnology. Bovine serum albumin BSA was obtained from Wako. The recombinant NTCP-His, at least in part, was suggested to be active from the results in scintillation proximity assay and AlphaScreen assay as already described Small molecules interacting with recombinant NTCP protein was screened by chemical arrays as described previously 30 , HBV inoculum used in this study was mainly prepared from the supernatant of Hep Nucleocapsid-associated DNA was extracted by digestion of free nucleic acids in cell lysate with DNase I and RNase A, followed by treatment with proteinase K as previously described Indirect immunofluorescence analysis was performed essentially as described previously using an anti-HBc antibody Thermofisher HBV replication was examined using Hep The bulk effect of DMSO was subtracted using reference flow cells.
The cells were then washed and lysed to measure the intracellular radioactivity by liquid scintillation counter. Ott, J. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Zeisel, M. Boettler, T. Glebe, D. Viral and cellular determinants involved in hepadnaviral entry. World journal of gastroenterology 13 , 22—38 Yan, H. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Blanchet, M.
Ko, C. Konig, A. Lucifora, J. Ezetimibe blocks hepatitis B virus infection after virus uptake into hepatocytes. Antiviral research 97 , — Nkongolo, S. Wang, X. Watashi, K. Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide NTCP. Hepatology Baltimore, Md. Iwamoto, M. Kaneko, M. Shimura, S. Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity.
Tsukuda, S. A new class of hepatitis B and D virus entry inhibitors, proanthocyanidin and its analogs, that directly act on the viral large surface proteins. Osada, H. Introduction of new tools for chemical biology research on microbial metabolites. Bioscience, biotechnology, and biochemistry 74 , — Kato, N. Construction of a microbial natural product library for chemical biology studies. Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide.
Chemical aspects of coumarin compounds for the prevention of hepatocellular carcinomas. Current medicinal chemistry. Anti-cancer agents. Barrera, A. Mapping of the hepatitis B virus pre-S1 domain involved in receptor recognition. Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes.
Gastroenterology , — Gripon, P. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein. Ishida, Y. Novel robust in vitro hepatitis B virus infection model using fresh human hepatocytes isolated from humanized mice. Ogura, N. Formation of covalently closed circular DNA in Hep Colpitts, C.
Dong, Z. Kawamura, T. Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival. Kawatani, M. Identification of matrix metalloproteinase inhibitors by chemical arrays.
Miyazaki, I. Robust and systematic drug screening method using chemical arrays and the protein library: identification of novel inhibitors of carbonic anhydrase II. Nakajima, Y. Identification and characterization of an inhibitor of trichothecene 3-O-acetyltransferase, TRI, by the chemical array approach. Noguchi, T. Hagiwara, K. Discovery of novel antiviral agents directed against the influenza A virus nucleoprotein using photo-cross-linked chemical arrays.
Identification of a novel Vpr-binding compound that inhibits HIV-1 multiplication in macrophages by chemical array. The application of the chemical array for biological study. Methods in molecular biology Clifton, N. Bogomolov, P. Petersen, J. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Journal of Biological Chemistry , — Download references.
The expression plasmids for preparing HCV pseudoparticles were kindly provided by Dr. Francois-Loic Cosset at University of Lyon. Osada, and K. Osada screened compounds in the chemical array. Ohashi, W.
Osada and K. Correspondence to Hiroyuki Osada or Koichi Watashi. Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Monica Ilies, PhD
Reprints and Permissions. Gastroenterology Frontiers in Microbiology Cellular and Molecular Life Sciences By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Advanced search. Skip to main content. Subjects Antiviral agents Hepatitis B. Introduction Hepatitis B virus HBV infection is a major public health problem, with an estimated million carriers worldwide 1. Figure 1. The fourth coordination position is occupied by water.
A fourth histidine is close to the water ligand, facilitating formation of Zn-OH center, which binds CO 2 to give a zinc bicarbonate. The active site also features a pocket suited for carbon dioxide, bringing it close to the hydroxide group. Carbonic anhydrase was initially found in the red blood cells of cows. These families have no significant amino acid sequence similarity and in most cases are thought to be an example of convergent evolution.
Vertebrates , algae and some bacteria have this family of CAs. The CA enzymes found in mammals are divided into four broad subgroups,  which, in turn consist of several isoforms:. Most prokaryotic and plant chloroplast CAs belong to the beta family. Two signature patterns for this family have been identified:. The gamma class of CAs come from methanogens , methane-producing bacteria that grow in hot springs.
The delta class of CAs has been described in diatoms. The distinction of this class of CA has recently  come into question, however. The zeta class of CAs occurs exclusively in bacteria in a few chemolithotrophs and marine cyanobacteria that contain cso- carboxysomes. Thus, the two forms may be distantly related, even though the underlying amino acid sequence has since diverged considerably. The eta family of CAs was recently found in organisms of the genus Plasmodium.
Several forms of carbonic anhydrase occur in nature. The primary function of the enzyme in animals is to interconvert carbon dioxide and bicarbonate to maintain acid-base balance in blood and other tissues, and to help transport carbon dioxide out of tissues. There are at least 14 different isoforms in mammals. In plants, carbonic anhydrase helps raise the concentration of CO 2 within the chloroplast in order to increase the carboxylation rate of the enzyme RuBisCO.
This is the reaction that integrates CO 2 into organic carbon sugars during photosynthesis , and can use only the CO 2 form of carbon, not carbonic acid or bicarbonate. However, this species of phytoplankton appears to have adapted to the low levels of zinc in the ocean by using cadmium when there is not enough zinc. This type of carbonic anhydrase is therefore cambialistic, meaning it can interchange the metal in its active site with other metals namely, zinc and cadmium.
The mechanism of cadmium carbonic anhydrase CDCA is essentially the same as that of other carbonic anhydrases in its conversion of carbon dioxide and water into bicarbonate and a proton. Unlike most other carbonic anhydrases, the active site metal ion is not bound by three histidine residues and a hydroxide ion. CDCA also has a three-dimensional folding structure that is unlike any other carbonic anhydrase, and its amino acid sequence is dissimilar to the other carbonic anhydrases.
Another key difference between CDCA and the other carbonic anhydrases is that CDCA has a mechanism for switching out its cadmium ion for a zinc ion in the event that zinc becomes more available to the phytoplankton than cadmium. The active site of CDCA is essentially "gated" by a chain of nine amino acids with glycine residues at positions 1 and 9. Normally, this gate remains closed and the cadmium ion is trapped inside. However, due to the flexibility and position of the glycine residues, this gate can be opened in order to remove the cadmium ion.
A zinc ion can then be put in its place and the gate will close behind it. The metal in the active site can be switched between zinc and cadmium depending on which one is more abundant at the time. Cadmium is still considered lethal to phytoplankton in high amounts. Studies have shown that T. The toxicity of the metal is reduced by the transcription and translation of phytochelatin , which are proteins that can bind and transport cadmium. Once bound by phytochelatin, cadmium is no longer toxic, and it can be safely transported to the CDCA enzyme.
Other phytoplankton from different water sources have been tested for the presence of CDCA.
In all species tested, CDCA-like proteins showed high levels of expression even in high concentrations of zinc and in the absence of cadmium. Carbonic anhydrase could in principle prove relevant to carbon capture. CA was placed in a N-methyldiethanolamine MDEA solution where it served to increase the concentration difference driving force of CO 2 between the flue stream of the power plant and liquid phase in a liquid-gas contactor.see url
Medicinal Chemistry Research Papers - qarirazonyqe.ml
From Wikipedia, the free encyclopedia. Carbonate dehydratase Ribbon diagram of human carbonic anhydrase II, with zinc ion visible in the center. See also: carbonic acid. Further information: Carbon capture and storage.