Search results for "Transmembrane"
showing 10 items of 299 documents
5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigat…
2017
Abstract A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683–4250 nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar–nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocycli…
N-Substituted and ring opened saccharin derivatives selectively inhibit transmembrane, tumor-associated carbonic anhydrases IX and XII.
2017
A series of N-substituted saccharins incorporating aryl, alkyl and alkynyl moieties, as well as some ring opened derivatives were prepared and investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The widespread cytosolic isoforms CA I and II were not inhibited by these sulfonamides whereas transmembrane, tumor-associated ones were effectively inhibited, with KIs in the range of 22.1-481nM for CA IX and of 3.9-245nM for hCA XII. Although the inhibition mechanism of these tertiary/secondary sulfonamides is unknown for the moment, the good efficacy and especially selectivity for the inhibition of the tumor-associated over the cytosolic, widespread isoforms, make…
The Evolutionary Conserved Transmembrane BAX Inhibitor Motif (TMBIM) Containing Protein Family Members 5 and 6 Are Essential for the Development and …
2021
Frontiers in cell and developmental biology 9, 666484 (2021). doi:10.3389/fcell.2021.666484 special issue: "Cell Death and Survival / You-Wen He, Speciality Chief Editor; Craig Michael Walsh, Speciality Chief Editor; Arm Ruhul Amin, Associate Editor; Gustavo P. Amarante-Mendes, Associate Editor"
Bis(imidazolium) salts derived from amino acids as receptors and transport agents for chloride anions
2015
The binding properties of bis(imidazolium) hosts 1a–c derived from amino acids towards different anions have been studied by 1H NMR titration experiments in 95 : 05 CD3CN : H2O at 303 K, ESI-MS and theoretical calculations. Among this family, the salt 1c showed a strong and high selectivity for chloride anions. Transmembrane chloride transport activity has also been studied for the three bis(imidazolium) based transporters in POPC liposome models, and compound 1a was identified as an active chloride/nitrate exchanger.
Genetic background in nonalcoholic fatty liver disease: A comprehensive review
2015
In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player i…
Gene structure and function of tyrosine kinases in the marine sponge Geodia cydonium: Autapomorphic characters of Metazoa
1999
Abstract Porifera (sponges) represent the most ancient, extant metazoan phylum. They existed already prior to the ‘Cambrian Explosion’. Based on the analysis of aa sequences of informative proteins, it is highly likely that all metazoan phyla evolved from only one common ancestor (monophyletic origin). As ‘autapomorphic’ proteins which are restricted to Metazoa only, integrin receptors, receptors with scavenger receptor cysteine-rich repeats, neuronal-like receptors and protein–tyrosine kinases (PTKs) have been identified in Porifera. From the marine sponge Geodia cydonium , a receptor tyrosine kinase (RTK) has been cloned that comprises the characteristic structural topology known from oth…
Isolation of theMNN9gene ofYarrowia lipolytica(YlMNN9) and phenotype analysis of a mutantylmnn9Δ strain
2003
In this work we describe the isolation of the Yarrowia lipolytica homologue of Saccharomyces cerevisiae MNN9 gene, which we have named YlMNN9, and the phenotype analysis of a Y. lipolytica strain containing the disrupted YlMNN9 allele. YlMNN9 was cloned using degenerate consensus oligonucleotides to generate specific probes that were in turn used to screen mini-gene libraries. The gene is defined by a 1014 bp ORF predicted to encode a protein 337 amino acids long that shares significant homology with the Mnn9ps of S. cerevisiae, Candida albicans and Hansenula polymorpha, including a putative N-terminal transmembrane domain. Disruption of YlMNN9 leads to phenotypes such as resistance to sodi…
Transgenic tools for proteomic analysis of ciliary transport
2015
Vision begins as photons are captured by photoreceptor cilia and light is converted into electrical signals that are then sent to the brain. As the photoreceptor cilium is not able to make its own proteins, all polypeptides needed for converting photons into electrical signals are synthetized in the cell body. How these molecules move from the cell body to cilia is still unclear. Opsin is one of the best-characterized transmembrane proteins. Our goal is to understand the mechanism of opsin transport into photoreceptor cilia. In this project, we use a combination of genetic and proteomic approaches in the zebrafish model. As the first step, we are constructing a transgenic line that expresse…
TMPRSS4 is a type II transmembrane serine protease involved in cancer and viral infections.
2012
Abstract Proteolytic enzymes are involved in almost all biological processes reflecting their importance in health and disease. The human genome contains nearly 600 protease-encoding genes forming more than 2% of the total human proteome. The serine proteases, with about 180 members, built the oldest and second largest family of human proteases. Ten years ago, a novel serine protease family named the type II transmembrane family (TTSP) was identified. This minireview summarizes the up-to-date knowledge about the still growing TTSPs, particularly focusing on the pathophysiological functions of the family member type II transmembrane serine protease (TMPRSS) 4. Recent studies provided importa…
The cGMP-gated channel of the rod photoreceptor — a new type of channel structure?
1990
Recents findings from Numa's laboratory reveal that there might exist a wider variety in channel protein structure than originally anticipated. Recently, the cloning has been reported of the first cGMP-gated ion channel, the vertebrate rod photoreceptor which is activated by cGMP acting from the inside of the rod outer segment membrane