Hb J- Meerut [alpha 120 (H3) Ala ->Glu (alpha1)] in a Turkish male.
Ontology highlight
ABSTRACT:
SUBMITTER: Dincol G
PROVIDER: S-EPMC1415838 | biostudies-literature | 2006
REPOSITORIES: biostudies-literature
Publications
Hb J- Meerut [alpha 120 (H3) Ala ->Glu (alpha1)] in a Turkish male.
Dinçol Gunçag G Güvenç Serkan S Elam Dedrey D Kutlar Abdullah A Kutlar Ferdane F
International journal of medical sciences 20060202 1
Hb J Meerut is an infrequently found alpha-globin variant. It has previously been reported in various populations around the world. One particular case reported in 1994 included a Turkish family. In this report, details of a second case of Hb J Meerut in a Turkish male who is unrelated to the first family are described. In the present case a slight increase in the oxygen affinity of Hb J Meerut, relative to that of the normal control, has been observed as detected by low p50 values in arterial w ...[more]
Similar Datasets
Project description:Salt bridges between oppositely charged side chains are well-known to stabilize protein structure, though their contributions vary considerably. Here we study Glu-Lys and Lys-Glu salt bridges, formed when the residues are spaced i, i + 4 surface of an isolated alpha-helix in aqueous solution. Both are stabilizing by -0.60 and -1.02 kcal/mol, respectively, when the interacting residues are fully charged. When the side chains are spaced i, i + 4, i + 8, forming a Glu-Lys-Glu triplet, the second salt bridge provides no additional stabilization to the helix. We attribute this to the inability of the central Lys to form two salt bridges simultaneously. Analysis of these salt bridges in protein structures shows that the Lys-Glu interaction is dominant, with the side chains of the Glu-Lys pair far apart.
| S-EPMC1560106 | biostudies-literature
Project description:Streptomyces lividans CelB is a family-12 endoglucanase that hydrolyses cellulose with retention of anomeric configuration. A recent X-ray structure of the catalytic domain at 1.75 A resolution has led to the preliminary assignment of Glu-120 and Glu-203 as the catalytic nucleophile and general acid-base respectively [Sulzenbacher, Shareck, Morosoli, Dupont and Davies (1997) Biochemistry 36, 16032-16039]. The present study confirms the identity of the nucleophile by trapping the glycosyl-enzyme intermediate with the mechanism-based inactivator 2', 4'-dinitrophenyl 2-deoxy-2-fluoro-beta-D-cellobioside (2FDNPC). The kinetics of inactivation proceeded in a saturable fashion, yielding the parameters kinact=0.29+/-0.02 min-1 and Kinact=0.72+/-0.08 mM. Uncompetitive inhibition was observed at high concentrations of 2FDNPC (Ki=9+/-1 mM), a behaviour that was also observed with the substrate 2',4'-dinitrophenyl beta-D-cellobioside (kcat=40+/-1 s-1, Km=0.35+/-0.03 mM, Ki=24+/-4 mM). Protection against inactivation was afforded by the competitive inhibitor cellobiose. The electrospray ionization (ESI) mass spectrum of the intact labelled CelB indicated that the inactivator had labelled the enzyme stoichiometrically. Reactivation of the trapped intermediate occurred spontaneously (kH2O=0.0022 min-1) or via transglycosylation, with cellobiose acting as an acceptor ligand (kreact=0.024 min-1, Kreact=54 mM). Digestion of the labelled enzyme by pepsin followed by LC-ESI-tandem MS (MS-MS) operating in neutral loss mode identified a labelled, singly charged peptide of m/z 947.5 Da. Isolation of this peptide by HPLC and subsequent collision-induced fragmentation by ESI-MS-MS produced a daughter-ion spectrum that corresponded to a sequence (QTEIM) containing Glu-120. The nucleophile Glu-120 and the putative acid-base catalyst Glu-203 are conserved in all known family-12 sequences.
| S-EPMC1219852 | biostudies-other
Project description:PepT1 is a di/tripeptide transporter highly expressed in the small intestine, but poorly or not expressed in the colon. However, during chronic inflammation, such as inflammatory bowel disease, PepT1 expression is induced in the colon. Commensal bacteria that colonize the human colon produce a large amount of di/tripeptides. To date, two bacterial peptides (N-formylmethionyl-leucyl-phenylalanine and muramyl dipeptide) have been identified as substrates of PepT1. We hypothesized that the proinflammatory tripeptide l-Ala-gamma-d-Glu-meso-DAP (Tri-DAP), a breakdown product of bacterial peptidoglycan, is transported into intestinal epithelial cells via PepT1. We found that uptake of glycine-sarcosine, a specific substrate of PepT1, in intestinal epithelial Caco2-BBE cells was inhibited by Tri-DAP in a dose-dependent manner. Tri-DAP induced activation of NF-kappaB and MAP kinases, consequently leading to production of the proinflammatory cytokine interleukin-8. Tri-DAP-induced inflammatory response in Caco2-BBE cells was significantly suppressed by silencing of PepT1 expression by using PepT1-shRNAs in a tetracycline-regulated expression (Tet-off) system. Colonic epithelial HT29-Cl.19A cells, which do not express PepT1 under basal condition, were mostly insensitive to Tri-DAP-induced inflammation. However, HT29-Cl.19A cells exhibited proinflammatory response to Tri-DAP upon stable transfection with a plasmid encoding PepT1. Accordingly, Tri-DAP significantly increased keratinocyte-derived chemokine production in colonic tissues from transgenic mice expressing PepT1 in intestinal epithelial cells. Finally, Tri-DAP induced a significant drop in intracellular pH in intestinal epithelial cells expressing PepT1, but not in cells that did not express PepT1. Our data collectively support the classification of Tri-DAP as a novel substrate of PepT1. Given that PepT1 is highly expressed in the colon during inflammation, PepT1-mediated Tri-DAP transport may occur more effectively during such conditions, further contributing to intestinal inflammation.
| S-EPMC2950691 | biostudies-literature
Project description:BackgroundThe L-Ala-D/L-Glu epimerases (AEEs), a subgroup of the enolase superfamily, catalyze the epimerization of L-Ala-D/L-Glu and other dipeptides in bacteria and contribute to the metabolism of the murein peptide of peptidoglycan. Although lacking in peptidoglycan, land plants possess AEE genes that show high similarity to those in bacteria.ResultsSimilarity searches revealed that the AEE gene is ubiquitous in land plants, from bryophytas to angiosperms. However, other eukaryotes, including green and red algae, do not contain genes encoding proteins with an L-Ala-D/L-Glu_epimerase domain. Homologs of land plant AEE genes were found to only be present in prokaryotes, especially in bacteria. Phylogenetic analysis revealed that the land plant AEE genes formed a monophyletic group with some bacterial homologs. In addition, land plant AEE proteins showed the highest similarity with these bacterial homologs and shared motifs only conserved in land plant and these bacterial AEEs. Integrated information on the taxonomic distribution, phylogenetic relationships and sequence similarity of the AEE proteins revealed that the land plant AEE genes were acquired from bacteria through an ancient horizontal gene transfer (HGT) event. Further evidence revealed that land plant AEE genes had undergone positive selection and formed the main characteristics of exon/intron structures through gaining some introns during the initially evolutionary period in the ancestor of land plants.ConclusionsThe results of this study clearly demonstrated that the ancestor of land plants acquired an AEE gene from bacteria via an ancient HGT event. Other findings illustrated that adaptive evolution through positive selection has contributed to the functional adaptation and fixation of this gene in land plants.
| S-EPMC3605383 | biostudies-literature
Project description:Several pathogenic bacteria have adopted effector proteins that, upon delivery into mammalian cells, undergo tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) or EPIYA-like sequence motif by host kinases such as Src family kinases (SFKs). This EPIYA phosphorylation triggers complex formation of bacterial effectors with SH2 domain-containing proteins that results in perturbation of host cell signaling and subsequent pathogenesis. Although the presence of such an anomalous protein interaction suggests the existence of a mammalian EPIYA-containing protein whose function is mimicked or subverted by bacterial EPIYA effectors, no molecule that uses the EPIYA motif for biological function has so far been reported in mammals. Here we show that mammalian Pragmin/SgK223 undergoes tyrosine phosphorylation at the EPIYA motif by SFKs and thereby acquires the ability to interact with the SH2 domain of the C-terminal Src kinase (Csk), a negative regulator of SFKs. The Pragmin-Csk interaction prevents translocalization of Csk from the cytoplasm to the membrane and subsequent inactivation of membrane-associated SFKs. As a result, SFK activity is sustained in cells where Pragmin is phosphorylated at the EPIYA motif. Because EPIYA phosphorylation of Pragmin is mediated by SFKs, cytoplasmic sequestration of Csk by Pragmin establishes a positive feedback regulation of SFK activation. Remarkably, the Helicobacter pylori EPIYA effector CagA binds to the Csk SH2 domain in place of Pragmin and enforces membrane recruitment of Csk and subsequent inhibition of SFKs. This work identifies Pragmin as a mammalian EPIYA effector and suggests that bacterial EPIYA effectors target Pragmin to subvert SFKs for successful infection.
| S-EPMC3169139 | biostudies-literature
Project description:The emergence and recurrence of ovarian cancer are associated with ovarian cancer stem cells. For cancer treatment, gene delivery of microbubbles (MB)-mediated microRNA (miRNA) is considered as a promising approach. In this study, our aim is to investigate the effects of MB-mediated let-7b-5p inhibitor on the proliferation and stemness characteristics of ovarian cancer (OVCA) cells. Let-7b-5p inhibitor mediated by MB was prepared (termed MB-let-7b-5p inhibitor), and the effects of MB-let-7b-5p inhibitor and let-7b-5p inhibitor on OVCA cell viability, proliferation and stemness characteristics were investigated. We found that MB-let-7b-5p inhibitor presented a higher transfection efficiency than let-7b-5p inhibitor alone. The inhibitory effect of MB-let-7b-5p inhibitor on OVCA cells was more significant than let-7b-5p inhibitor. Let-7b-5p targeted DEAD (Asp-Glu-Ala-Asp)-box helicase 19A (DDX19A), which was downregulated in OVCA cells. The downregulation of DDX19A reversed the inhibitory effects of MB-let-7b-5p inhibitor on OVCA cells. To sum up, we found that MB-let-7b-5p suppressed OVCA cell malignant behaviors by targeting DDX19A.
| S-EPMC8806929 | biostudies-literature
Project description:BACKGROUND AND PURPOSE: Alpha(1)-adrenoceptor antagonists are extensively used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia. Among the side effects, ejaculatory dysfunction occurs more frequently with drugs that are relatively selective for alpha(1A)-adrenoceptors compared with other drugs of this class. This suggests that alpha(1A)-adrenoceptors may contribute to ejaculation. However, this has not been studied at the molecular level. EXPERIMENTAL APPROACH: The physiological contribution of each alpha(1)-adrenoceptor subtype was characterized using alpha(1)-adrenoceptor subtype-selective knockout (KO) mice (alpha(1A)-, alpha(1B)- and alpha(1D)-AR KO mice) since the subtype-specific drugs available are only moderately selective. We analysed the role of alpha(1)-adrenoceptors in the blood pressure and vascular response as well as ejaculation by determining these variables in alpha(1)-adrenoceptor subtype-selective KO mice and in mice with all their alpha(1)-adrenoceptor subtypes deleted (alpha(1)-AR triple-KO mice). KEY RESULTS: The pregnancy rate was reduced by 50% in alpha(1A)-adrenoceptor KO mice, and this reduction was dramatically enhanced in alpha(1)-adrenoceptor triple-KO mice. Contractile tension of the vas deferens in response to noradrenaline was markedly decreased in alpha(1A)-adrenoceptor KO mice, and this contraction was completely abolished in alpha(1)-adrenoceptor triple-KO mice. This attenuation of contractility was also observed in the electrically stimulated vas deferens. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that alpha(1)-adrenoceptors, particularly alpha(1A)-adrenoceptors, are required for normal contractility of the vas deferens and consequent sperm ejaculation as well as having a function in fertility.
| S-EPMC2042949 | biostudies-other
Project description:Members of the P(4) subfamily of P-type ATPases are believed to catalyze flipping of phospholipids across cellular membranes, in this way contributing to vesicle biogenesis in the secretory and endocytic pathways. P(4)-ATPases form heteromeric complexes with Cdc50-like proteins, and it has been suggested that these act as beta-subunits in the P(4)-ATPase transport machinery. In this work, we investigated the role of Cdc50-like beta-subunits of P(4)-ATPases for targeting and function of P(4)-ATPase catalytic alpha-subunits. We show that the Arabidopsis P(4)-ATPases ALA2 and ALA3 gain functionality when coexpressed with any of three different ALIS Cdc50-like beta-subunits. However, the final cellular destination of P(4)-ATPases as well as their lipid substrate specificity are independent of the nature of the ALIS beta-subunit they were allowed to interact with.
| S-EPMC2828965 | biostudies-literature
Project description:We identified two new variants in the third exon of the α-globin gene in families from southern Italy: the Hb Rogliano, α1 cod108 ACC>AAC or α1[α108(G15)Thr→Asn] and the Hb Policoro, α2 cod124 TCC>CCC or α2[α124(H7)Ser→Pro]. The carriers showed mild α-thalassemia phenotype and abnormal hemoglobin stability features. These mutations occurred in the G and H helices of the α-globin both involved in the specific recognition of AHSP and β1 chain. Molecular characterization of mRNA, globin chain analyses and molecular modelling studies were carried out to highlight the mechanisms causing the α-thalassemia phenotype. The results demonstrated that the α-thalassemia defect associated with the two Hb variants originated by different defects. Hb Rogliano showed an intrinsic instability of the tetramer due to anomalous intra- and inter-chain interactions suggesting that the variant chain is normally synthesized and complexed with AHSP but rapidly degraded because it is unable to form the α1β1 dimers. On the contrary in the case of Hb Policoro two different molecular mechanisms were shown: the reduction of the variant mRNA level by an unclear mechanism and the protein instability due to impairment of AHSP interaction. These data highlighted that multiple approaches, including mRNA quantification, are needed to properly identify the mechanisms leading to the α-thalassemia defect. Elucidation of the specific mechanism leads to the definition of a given phenotype providing important guidance for the diagnosis of unstable variants.
| S-EPMC4346585 | biostudies-literature
Project description:It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary α-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.
| S-EPMC7278601 | biostudies-literature