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11.
Hye-Lim KimMi-Bee Park Yumin KimYun Gyeong Yang Soo-Woong LeeNingning Zhuang Kon Ho Lee Young Shik Park 《FEBS letters》2012,586(20):3596-3600
We have studied the regulatory function of Dictyostelium discoideum Ax2 phenylalanine hydroxylase (dicPAH) via characterization of domain structures. Including the full-length protein, partial proteins truncated in regulatory, tetramerization, or both, were prepared from Escherichia coli as his-tag proteins and examined for oligomeric status and catalytic parameters for phenylalanine. The proteins were also expressed extrachromosomally in the dicPAH knockout strain to examine their in vivo compatibility. The results suggest that phenylalanine activates dicPAH, which is functional in vivo as a tetramer, although cooperativity was not observed. In addition, the results of kinetic study suggest that the regulatory domain of dicPAH may play a role different from that of the domain in mammalian PAH.
Structured summary of protein interactions
dicPAH and dicPAHbind by molecular sieving (View Interaction: 1, 2, 3, 4) 相似文献12.
Jayalakshmi Kumpati 《Biochemical and biophysical research communications》1982,105(2):482-487
To investigate the role of phenylalanine and tryptophane as potential antisickling agents in intact human SS-red blood cells a liposomal transport system was employed to transfer phenyl-alanine or tryptophane into intact SS-red blood cells. Aromatic amino acids and short peptides containing phenylalanine have been demonstrated to increase the minimum gelling concentration and solubility of deoxy-hemoglobin S in aqueous solution. However, these compounds do not cross the red blood cell membrane under usual incubation conditions. Incorporation of phenylalanine or tryptophane into intact SS-red blood cells liposomal transport system markedly inhibited the sickling of deoxy-hemoglobin S. These findings raise the possibility that a nontoxic liposomal transport system which facilitates incorporation of antisickling agents into intact SS-RBC may have significant therapeutic implications in the treatment of sickle cell disease. 相似文献
13.
14.
Thanthrige Thiunuwan Priyathilaka Don Anushka Sandaruwan Elvitigala Ilson Whang Bong-Soo Lim Hyung-Bok Jeong Sang-Yeob Yeo Cheol Young Choi Jehee Lee 《Gene》2014
Toll-like receptors (TLRs) are a large family of pattern recognition receptors, which are involved in triggering host immune responses against various pathogens by detecting their evolutionarily conserved pathogen associated molecular patterns (PAMPs). TLR21 is a non-mammalian type TLR, which recognizes unmethylated CpG DNA, and is considered as a functional homolog of mammalian TLR9. In this study, we attempted to identify and characterize a novel TLR21 counterpart from rock bream (Oplegnathus fasciatus) designated as RbTLR21, at molecular level. The complete coding sequence of RbTLR21 was 2919 bp in length, which encodes a polypeptide of 973 amino acids with a predicted molecular mass of 112 kDa and a theoretical isoelectric point of 8.6. The structure of the deduced RbTLR21 protein is similar to that of the members of typical TLR family, and includes the ectodomain, which consists of 16 leucine rich repeats (LRRs), a transmembrane domain, and a cytoplasmic Toll/interleukin-1 receptor (TIR) domain. According to the pairwise sequence analysis data, RbTLR21 was homologous to that of the orange-spotted grouper (Epinephelus coioides) with 76.9% amino acid identity. Furthermore, our phylogenetic analysis revealed that RbTLR21 is closely related to E. coioides TLR21. The RbTLR21 was ubiquitously expressed in all the tissues tested, but the highest expression was found in spleen. Additionally, upon stimulation with Streptococcus iniae, rock bream iridovirus (RBIV), and Edwardsiella tarda, RbTLR21 mRNA was significantly up-regulated in spleen tissues. Collectively, our findings suggest that RbTLR21 is indeed an ortholog of the TLR21 family and may be important in mounting host immune responses against pathogenic infections. 相似文献
15.
Effects of DGAT1 and GHR on milk yield and milk composition in the Chinese dairy population 总被引:1,自引:0,他引:1
Previous studies have demonstrated that the p.Lys232Ala substitution in the acylCoA: diacylglycerol acyltransferase ( DGAT1 ) gene and the p.Phe279Tyr mutation in the growth hormone receptor ( GHR ) gene are the causative quantitative trait loci underlying milk yield and composition on BTA14 and BTA20 respectively. To examine their applications in the genetic improvement of Chinese dairy cattle productivity, we herein investigated the effects of the DGAT1 p.Lys232Ala and GHR p.Phe279Tyr mutations on milk, fat and protein yield, as well as fat and protein percentage in the milk of 1222 Holstein cows. Genotyping was performed using PCR-RFLP for DGAT1 or primer-introduced restriction analysis (PCR-PIRA) for GHR . With a mixed animal model, the significant associations of the DGAT1 p.Lys232Ala substitution with 305-day milk, fat and protein yield were identified ( P = 0.0001). The DGAT1 allele that encode lysine at position 232 was associated with increased 305-day milk fat yield, but with decreased 305-day milk and protein yield, whereas the GHR p.Phe279Tyr mutation was found to be significantly associated with protein percentage ( P = 0.0014). The allele substitution effect of p.279Phe by p.279Tyr may lead to a significant increase in protein percentage. Our findings indicate that DGAT1 p.232Ala and GHR p.279Phe could be used to increase milk yield and protein yield of Chinese Holstein cows. 相似文献
16.
Xuan Qiu Kuanzhi Liu Lin Xiao Sheng Jin Jinghui Dong Xu Teng Qi Guo Yuhong Chen Yuming Wu 《生物化学与生物物理学报:疾病的分子基础》2018,1864(11):3723-3738
Dysfunctional vascular smooth muscle (VSM) plays a vital role in the process of atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Alpha-lipoic acid (ALA) can prevent the altered VSM induced by diabetes. However, the precise mechanism underlying the beneficial effect of ALA is not well understood. This study aimed to determine whether ALA ameliorates VSM function by elevating hydrogen sulfide (H2S) level in diabetes and whether this effect is associated with regulation of autophagy of VSM cells (VSMCs). We found decreased serum H2S levels in Chinese patients and rats with type 2 diabetes mellitus (T2DM). ALA treatment could increase H2S level, which reduced the autophagy-related index and activation of the 5′-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, thereby protecting vascular function in rats with T2DM. Propargylglycine (PPG), a cystathionine-γ-lyase inhibitor, could weaken the ALA effect. In cultured VSMCs, high glucose level also reduced H2S level, upregulated the autophagy-related index and activated the AMPK/mTOR pathway, which were reversed by concomitant application of sodium hydrosulfide (NaHS, an H2S donor) or ALA. The protective effect of NaHS or ALA was attenuated by rapamycin (an autophagy activator), 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (an AMPK activator) or PPG. In contrast, Compound C (an AMPK inhibitor) enhanced the effect of ALA or NaHS. ALA may have a protective effect on VSMCs in T2DM by elevating H2S level and downregulating autophagy via the AMPK/mTOR pathway. This study provides a new target for addressing diabetic macroangiopathy. 相似文献
17.
Hee Kyoung Chung Eun Mi Ko Sung Woo Kim Sung-June Byun Hak-Jae Chung Moosik Kwon Hwi-Cheul Lee Byoung-Chul Yang Deug-Woo Han Jin-Ki Park Sung-Gu Hong Won-Kyong Chang Kyung-Woon Kim 《BMB reports》2012,45(12):742-747
Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent (H2O2). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure. [BMB Reports 2012; 45(12): 742-747] 相似文献
18.
Erwin P.P. Vos 《生物化学与生物物理学报:生物膜》2009,1788(2):581-25331
This paper presents domain complementation studies in the mannitol transporter, EIImtl, from Escherichia coli. EIImtl is responsible for the transport and concomitant phosphorylation of mannitol over the cytoplasmic membrane. By using tryptophan-less EIImtl as a basis, each of the four phenylalanines located in the cytoplasmic loop between putative transmembrane helices II and III in the membrane-embedded C domain were replaced by tryptophan, yielding the mutants W97, W114, W126, and W133. Except for W97, these single-tryptophan mutants exhibited a high, wild-type-like, binding affinity for mannitol. Of the four mutants, only W114 showed a high mannitol phosphorylation activity. EIImtl is functional as a dimer and the effect of these mutations on the oligomeric activity was investigated via heterodimer formation (C/C domain complementation studies). The low phosphorylation activities of W126 and W133 could be increased 7-28 fold by forming heterodimers with either the C domain of W97 (IICmtlW97) or the inactive EIImtl mutant G196D. W126 and W133, on the other hand, did not complement each other. This study points towards a role of positions 97, 126 and 133 in the oligomeric activation of EIImtl. The involvement of specific residue positions in the oligomeric functioning of a sugar-translocating EII protein has not been presented before. 相似文献
19.
The aim of this study was to clarify the role of the actin cytoskeleton during chemotactic peptide fMet-Leu-Phe (fMLF)-stimulated respiratory burst in human neutrophil granulocytes. Reactive oxygen species (ROS) was measured as luminol-amplified chemiluminescence (CL) and F-actin content as bodipy phallacidin fluorescence in neutrophils treated with latrunculin B or jasplakinolide, an inhibitor and activator of actin polymerization, respectively. Latrunculin B markedly decreased, whereas jasplakinolide increased, the F-actin content in neutrophils, unstimulated or stimulated with fMLF. Latrunculin B enhanced the fMLF-triggered ROS-production more than tenfold. Jasplakinolide initially inhibited the fMLF-induced CL-response, however, caused a potent second sustained phase (>400% of control). Both actin drugs triggered a substantial CL-response when added 5-25 min after fMLF. This was also valid for chemotactic doses of fMLF, where latrunculin B and jasplakinolide amplified the ROS-production 5-10 times. By using specific signal transduction inhibitors, we found that the NADPH oxidase activation triggered by destabilization of the actin cytoskeleton occurs downstream of phospholipase C and protein kinase C but is mediated by Rho GTPases and tyrosine phosphorylation. In conclusion, rearrangements of the actin cytoskeleton are a prerequisite in connecting ligand/receptor activation, generation of second messengers and assembly of the NADPH oxidase in neutrophil granulocytes. 相似文献
20.
Emil Polak Andrej Ficek Jan Radvanszky Andrea Soltysova Otto Urge Eleonora Cmelova Dana Kantarska Ludevit Kadasi 《Gene》2013
We investigated the mutation spectrum of the phenylalanine hydroxylase gene (PAH) in a cohort of patients from 135 Slovak PKU families. Mutational screening of the known coding region, including conventional intron splice sites, was performed using high-resolution melting analysis, with subsequent sequencing analysis of the samples showing deviated melting profiles compared to control samples. The PAH gene was also screened for deletions and duplications using MLPA analysis. Forty-eight different disease causing mutations were identified in our patient group, including 30 missense, 8 splicing, 7 nonsense, 2 large deletions and 1 small deletion with frameshift; giving a detection rate of 97.6%. The most prevalent mutation was the p.R408W, occurring in 47% of all alleles, which concurs with results from neighboring and other Slavic countries. Other frequent mutations were: p.R158Q (5.3%), IVS12 + 1G>A (5.3%), p.R252W (5.1%), p.R261Q (3.9%) and p.A403V (3.6%). We also identified three novel missense mutations: p.F233I, p.R270I, p.F331S and one novel variant: c.− 30A>T in the proximal part of the PAH gene promoter. A spectrum of 84 different genotypes was observed and a genotype based predictions of BH4-responsiveness were assessed. Among all genotypes, 36 were predicted to be BH4-responsive represented by 51 PKU families. In addition, genotype–phenotype correlations were performed. 相似文献