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[PMID]:28864672
[Au] Autor:Hobbs C; Reid JD; Shepherd M
[Ad] Endereço:School of Biosciences, University of Kent, Canterbury CT2 7NJ, U.K.
[Ti] Título:The coproporphyrin ferrochelatase of : mechanistic insights into a regulatory iron-binding site.
[So] Source:Biochem J;474(20):3513-3522, 2017 Oct 10.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The majority of characterised ferrochelatase enzymes catalyse the final step of classical haem synthesis, inserting ferrous iron into protoporphyrin IX. However, for the recently discovered coproporphyrin-dependent pathway, ferrochelatase catalyses the penultimate reaction where ferrous iron is inserted into coproporphyrin III. Ferrochelatase enzymes from the bacterial phyla Firmicutes and Actinobacteria have previously been shown to insert iron into coproporphyrin, and those from and are known to be inhibited by elevated iron concentrations. The work herein reports a (coproporphyrin III) for ferrochelatase of 1.5 µM and it is shown that elevating the iron concentration increases the for coproporphyrin III, providing a potential explanation for the observed iron-mediated substrate inhibition. Together, structural modelling, site-directed mutagenesis, and kinetic analyses confirm residue Glu271 as being essential for the binding of iron to the inhibitory regulatory site on ferrochelatase, providing a molecular explanation for the observed substrate inhibition patterns. This work therefore has implications for how haem biosynthesis in is regulated by iron availability.
[Mh] Termos MeSH primário: Coproporfirinas/metabolismo
Ferroquelatase/metabolismo
Ferro/metabolismo
Staphylococcus aureus/enzimologia
[Mh] Termos MeSH secundário: Sítios de Ligação/fisiologia
Coproporfirinas/química
Ferroquelatase/química
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coproporphyrins); E1UOL152H7 (Iron); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170362


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[PMID]:28784691
[Au] Autor:Lam WKJ; Gai W; Sun K; Wong RSM; Chan RWY; Jiang P; Chan NPH; Hui WWI; Chan AWH; Szeto CC; Ng SC; Law MF; Chan KCA; Chiu RWK; Lo YMD
[Ad] Endereço:Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
[Ti] Título:DNA of Erythroid Origin Is Present in Human Plasma and Informs the Types of Anemia.
[So] Source:Clin Chem;63(10):1614-1623, 2017 Oct.
[Is] ISSN:1530-8561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There is much interest in the tissue of origin of circulating DNA in plasma. Data generated using DNA methylation markers have suggested that hematopoietic cells of white cell lineages are important contributors to the circulating DNA pool. However, it is not known whether cells of the erythroid lineage would also release DNA into the plasma. METHODS: Using high-resolution methylation profiles of erythroblasts and other tissue types, 3 genomic loci were found to be hypomethylated in erythroblasts but hypermethylated in other cell types. We developed digital PCR assays for measuring erythroid DNA using the differentially methylated region for each locus. RESULTS: Based on the methylation marker in the ferrochelatase gene, erythroid DNA represented a median of 30.1% of the plasma DNA of healthy subjects. In subjects with anemia of different etiologies, quantitative analysis of circulating erythroid DNA could reflect the erythropoietic activity in the bone marrow. For patients with reduced erythropoietic activity, as exemplified by aplastic anemia, the percentage of circulating erythroid DNA was decreased. For patients with increased but ineffective erythropoiesis, as exemplified by ß-thalassemia major, the percentage was increased. In addition, the plasma concentration of erythroid DNA was found to correlate with treatment response in aplastic anemia and iron deficiency anemia. Plasma DNA analysis using digital PCR assays targeting the other 2 differentially methylated regions showed similar findings. CONCLUSIONS: Erythroid DNA is a hitherto unrecognized major component of the circulating DNA pool and is a noninvasive biomarker for differential diagnosis and monitoring of anemia.
[Mh] Termos MeSH primário: Anemia/sangue
Anemia/genética
Metilação de DNA
DNA/sangue
DNA/genética
Eritroblastos/patologia
[Mh] Termos MeSH secundário: Anemia/diagnóstico
Anemia/patologia
Anemia Aplástica/sangue
Anemia Aplástica/diagnóstico
Anemia Aplástica/genética
Anemia Aplástica/patologia
Anemia Ferropriva/sangue
Anemia Ferropriva/diagnóstico
Anemia Ferropriva/genética
Anemia Ferropriva/patologia
Diagnóstico Diferencial
Eritroblastos/metabolismo
Eritropoese
Ferroquelatase/genética
Seres Humanos
Síndromes Mielodisplásicas/sangue
Síndromes Mielodisplásicas/diagnóstico
Síndromes Mielodisplásicas/genética
Síndromes Mielodisplásicas/patologia
Talassemia beta/sangue
Talassemia beta/diagnóstico
Talassemia beta/genética
Talassemia beta/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9007-49-2 (DNA); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1373/clinchem.2017.272401


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[PMID]:28614581
[Au] Autor:Balwani M; Naik H; Anderson KE; Bissell DM; Bloomer J; Bonkovsky HL; Phillips JD; Overbey JR; Wang B; Singal AK; Liu LU; Desnick RJ
[Ad] Endereço:Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.
[Ti] Título:Clinical, Biochemical, and Genetic Characterization of North American Patients With Erythropoietic Protoporphyria and X-linked Protoporphyria.
[So] Source:JAMA Dermatol;153(8):789-796, 2017 Aug 01.
[Is] ISSN:2168-6084
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Autosomal recessive erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare photodermatoses presenting with variable degrees of painful phototoxicity that markedly affects quality of life. The clinical variability, determinants of severity, and genotype/phenotype correlations of these diseases are not well characterized. Objective: To describe the baseline clinical characteristics, genotypes, and determinants of disease severity in a large patient cohort with EPP or XLP. Design, Setting, and Participants: A prospective observational study was conducted among patients with confirmed diagnoses of EPP or XLP from November 1, 2010, to December 6, 2015, at 6 academic medical centers of the Porphyrias Consortium of the National Institutes of Health Rare Diseases Clinical Research Network. Detailed medical histories, including history of phototoxicity and treatment, were collected on standardized case report forms. Patients underwent baseline laboratory testing, total erythrocyte protoporphyrin (ePPIX) testing, and molecular genetic testing. Data were entered into a centralized database. Main Outcomes and Measures: Results of biochemical and genetic tests were explored for association with clinical phenotype in patients with EPP or XLP. Results: Of the 226 patients in the study (113 female and 113 male patients; mean [SD] age, 36.7 [17.0] years), 186 (82.3%) had EPP with a FECH (OMIM 612386) mutation and the common low-expression FECH allele IVS3-48T>C, and only 1 patient had 2 FECH mutations. Twenty-two patients had XLP (9.7%; 10 male and 12 female patients), and 9 patients (4.0%) had elevated ePPIX levels and symptoms consistent with protoporphyria but no detectable mutation in the FECH or ALAS2 (OMIM 301300) gene. Samples of DNA could not be obtained from 8 patients. Patients' mean (SD) age at symptom onset was 4.4 (4.4) years. Anemia (107 [47.3%]), history of liver dysfunction (62 [27.4%]), and gallstones (53 [23.5%]) were commonly reported. Higher ePPIX levels were associated with earlier age of symptom onset (median ePPIX levels for those who developed symptoms before vs after 1 year of age, 1744 vs 1567 µg/dL; P = .02), less sun tolerance (median ePPIX levels for those reporting symptoms before vs after 10 minutes of sun exposure, 2233 vs 1524 µg/dL; P ≤ .001), and increased risk of liver dysfunction (median ePPIX levels for those with liver dysfunction vs normal liver function, 2016 vs 1510 µg/dL; P = .003). Patients with EPP and FECH missense mutations had significantly lower ePPIX levels than those with other mutations (1462 vs 1702 µg/dL; P = .01). Male patients with XLP had significantly higher ePPIX levels, on average, than did patients with EPP (3574 vs 1669 µg/dL; P < .001). Marked clinical variability was seen in female patients with XLP owing to random X-chromosomal inactivation. Conclusions and Relevance: These data suggest that higher ePPIX levels are a major determinant of disease severity and risk of liver dysfunction in patients with EPP or XLP. These findings provide a framework for clinical monitoring and management of these disorders.
[Mh] Termos MeSH primário: 5-Aminolevulinato Sintetase/deficiência
Ferroquelatase/genética
Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia
Protoporfiria Eritropoética/fisiopatologia
Qualidade de Vida
[Mh] Termos MeSH secundário: 5-Aminolevulinato Sintetase/genética
Adolescente
Adulto
Idoso
Criança
Pré-Escolar
Feminino
Doenças Genéticas Ligadas ao Cromossomo X/genética
Genótipo
Seres Humanos
Hepatopatias/genética
Hepatopatias/fisiopatologia
Masculino
Meia-Idade
Mutação
Fenótipo
Estudos Prospectivos
Protoporfiria Eritropoética/genética
Índice de Gravidade de Doença
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
EC 2.3.1.37 (5-Aminolevulinate Synthetase); EC 2.3.1.37 (ALAS2 protein, human); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE
[do] DOI:10.1001/jamadermatol.2017.1557


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[PMID]:28412459
[Au] Autor:Steinkellner H; Singh HN; Muckenthaler MU; Goldenberg H; Moganty RR; Scheiber-Mojdehkar B; Sturm B
[Ad] Endereço:Department of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Vienna, Austria; Department of Medical Genetics, Medical University of Vienna, Vienna, Austria.
[Ti] Título:No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells.
[So] Source:Gene;621:5-11, 2017 Jul 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the protein frataxin. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid progenitor stem cells obtained from FRDA patients and healthy donors to investigate the putative role, if any, of frataxin deficiency in heme synthesis. We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA quantification. We used atomic absorption spectrophotometry for iron levels and a photometric assay for hemoglobin levels. Protoporphyrin IX and Ferrochelatase were analyzed using auto-fluorescence. An "IronChip" microarray analysis followed by a protein-protein interaction analysis was performed. FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis. The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported.
[Mh] Termos MeSH primário: Células Precursoras Eritroides/metabolismo
Eritropoese
Ataxia de Friedreich/metabolismo
Heme/biossíntese
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Células Cultivadas
Células Precursoras Eritroides/citologia
Ferroquelatase/metabolismo
Ataxia de Friedreich/sangue
Hemoglobinas/metabolismo
Seres Humanos
Ferro/metabolismo
Proteínas de Ligação ao Ferro/genética
Proteínas de Ligação ao Ferro/metabolismo
Estresse Oxidativo
Protoporfirinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hemoglobins); 0 (Iron-Binding Proteins); 0 (Protoporphyrins); 0 (frataxin); 42VZT0U6YR (Heme); C2K325S808 (protoporphyrin IX); E1UOL152H7 (Iron); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170615
[Lr] Data última revisão:
170615
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170417
[St] Status:MEDLINE


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[PMID]:28185024
[Au] Autor:Barman-Aksoezen J; Girelli D; Aurizi C; Schneider-Yin X; Campostrini N; Barbieri L; Minder EI; Biolcati G
[Ad] Endereço:Institute for Laboratory Medicine, Stadtspital Triemli, Zürich, Switzerland.
[Ti] Título:Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity.
[So] Source:J Inherit Metab Dis;40(3):433-441, 2017 May.
[Is] ISSN:1573-2665
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Patients with erythropoietic protoporphyria (EPP) have reduced activity of the enzyme ferrochelatase that catalyzes the insertion of iron into protoporphyrin IX (PPIX) to form heme. As the result of ferrochelatase deficiency, PPIX accumulates and causes severe photosensitivity. Among different patients, the concentration of PPIX varies considerably. In addition to photosensitivity, patients frequently exhibit low serum iron and a microcytic hypochromic anemia. The aims of this study were to (1) search for factors related to PPIX concentration in EPP, and (2) characterize anemia in EPP, i.e., whether it is the result of an absolute iron deficiency or the anemia of chronic disease (ACD). Blood samples from 67 EPP patients (51 Italian and 16 Swiss) and 21 healthy volunteers were analyzed. EPP patients had lower ferritin (p = 0.021) and hepcidin (p = 0.031) concentrations and higher zinc-protoporphyrin (p < 0.0001) and soluble-transferrin-receptor (p = 0.0007) concentrations compared with controls. This indicated that anemia in EPP resulted from an absolute iron deficiency. Among EPP patients, PPIX concentrations correlated with both growth differentiation factor (GDF) 15 (p = 0.012) and male gender (p = 0.015). Among a subgroup of patients who were iron replete, hemoglobin levels were normal, which suggested that iron but not ferrochelatase is the limiting factor in heme synthesis of individuals with EPP.
[Mh] Termos MeSH primário: Fator 15 de Diferenciação de Crescimento/metabolismo
Ferro/metabolismo
Protoporfiria Eritropoética/metabolismo
[Mh] Termos MeSH secundário: Anemia Hipocrômica/metabolismo
Estudos de Casos e Controles
Eritrócitos/metabolismo
Feminino
Ferritinas/metabolismo
Ferroquelatase/metabolismo
Hemoglobinas/metabolismo
Hepcidinas/metabolismo
Seres Humanos
Masculino
Transtornos de Fotossensibilidade/metabolismo
Protoporfirinas/metabolismo
Índice de Gravidade de Doença
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GDF15 protein, human); 0 (Growth Differentiation Factor 15); 0 (Hemoglobins); 0 (Hepcidins); 0 (Protoporphyrins); 9007-73-2 (Ferritins); C2K325S808 (protoporphyrin IX); E1UOL152H7 (Iron); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE
[do] DOI:10.1007/s10545-017-0017-7


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[PMID]:28054335
[Au] Autor:Alagappan U; Pramono ZA; Chong WS
[Ad] Endereço:Department of Dermatology, Changi General Hospital, Singapore.
[Ti] Título:Ferrochelatase gene mutation in Singapore and a novel frame-shift mutation in an Asian boy with erythropoietic protoporphyria.
[So] Source:Int J Dermatol;56(3):272-276, 2017 Mar.
[Is] ISSN:1365-4632
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused by decreased activity of the enzyme ferrochelatase (FECH ). The frequency of the hypomorphic c.333-48C allele in a population directly contributes to the prevalence of EPP in the same population. This study sought to identify the molecular basis of EPP in a Chinese patient from Singapore and the c.333-48C allele frequency among the Chinese population in Singapore. MATERIALS AND METHODS: FECH gene was screened for mutation in the patient's DNA sample by polymerase chain reaction amplification and DNA sequencing. To validate the identified mutation, the FECH region harboring the mutation was screened in DNA samples from all healthy controls. One patient and 46 ethnically matched healthy controls were included in the study. RESULTS: A novel c.474dupC which leads to a frameshift and premature stop codon was identified in one allele, while the other allele showed to carry c.333-48C and c.337C>T variants in the patient's FECH. The frequency of the c.333-48C hypomorphic allele is 27% among Chinese population in Singapore. CONCLUSIONS: c.474dupC in one allele trans to hypomorphic c.333-48C and c.337C>T allele in FECH gene may be the underlying cause of the clinical EPP of the studied patient. The FECH hypomorphic c.333-48C allele frequency in Singapore is lower than the Han Chinese (41.3%) and Japanese (43%) populations but nearly the same as the Southeast Asian (31%) population and higher than the European (2.7-11%) population.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Ferroquelatase/genética
Protoporfiria Eritropoética/genética
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Criança
Análise Mutacional de DNA
Mutação da Fase de Leitura
Frequência do Gene
Seres Humanos
Masculino
Singapura
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE
[do] DOI:10.1111/ijd.13418


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[PMID]:27998984
[Au] Autor:Taylor NG; Swenson S; Harris NJ; Germany EM; Fox JL; Khalimonchuk O
[Ad] Endereço:From the Department of Chemistry and Biochemistry, College of Charleston, Charleston, South Carolina 29424 and.
[Ti] Título:The Assembly Factor Pet117 Couples Heme a Synthase Activity to Cytochrome Oxidase Assembly.
[So] Source:J Biol Chem;292(5):1815-1825, 2017 Feb 03.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Heme a is an essential metalloporphyrin cofactor of the mitochondrial respiratory enzyme cytochrome c oxidase (CcO). Its synthesis from heme b requires several enzymes, including the evolutionarily conserved heme a synthase (Cox15). Oligomerization of Cox15 appears to be important for the process of heme a biosynthesis and transfer to maturing CcO. However, the details of this process remain elusive, and the roles of any additional CcO assembly factors that may be involved remain unclear. Here we report the systematic analysis of one such uncharacterized assembly factor, Pet117, and demonstrate in Saccharomyces cerevisiae that this evolutionarily conserved protein is necessary for Cox15 oligomerization and function. Pet117 is shown to reside in the mitochondrial matrix, where it is associated with the inner membrane. Pet117 functions at the later maturation stages of the core CcO subunit Cox1 that precede Cox1 hemylation. Pet117 also physically interacts with Cox15 and specifically mediates the stability of Cox15 oligomeric complexes. This Cox15-Pet117 interaction observed by co-immunoprecipitation persists in the absence of heme a synthase activity, is dependent upon Cox1 synthesis and early maturation steps, and is further dependent upon the presence of the matrix-exposed, unstructured linker region of Cox15 needed for Cox15 oligomerization, suggesting that this region mediates the interaction or that the interaction is lost when Cox15 is unable to oligomerize. Based on these findings, it was concluded that Pet117 mediates coupling of heme a synthesis to the CcO assembly process in eukaryotes.
[Mh] Termos MeSH primário: Complexo IV da Cadeia de Transporte de Elétrons/metabolismo
Ferroquelatase/metabolismo
Proteínas de Membrana/metabolismo
Multimerização Proteica/fisiologia
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Complexo IV da Cadeia de Transporte de Elétrons/genética
Ferroquelatase/genética
Proteínas de Membrana/genética
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (COX15 protein, S cerevisiae); 0 (Membrane Proteins); 0 (Saccharomyces cerevisiae Proteins); EC 1.9.3.1 (Cox1 protein, S cerevisiae); EC 1.9.3.1 (Electron Transport Complex IV); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161222
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.766980


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[PMID]:27966701
[Au] Autor:Li M; Lightfoot HL; Halloy F; Malinowska AL; Berk C; Behera A; Schümperli D; Hall J
[Ad] Endereço:Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. jonathan.hall@pharma.ethz.ch.
[Ti] Título:Synthesis and cellular activity of stereochemically-pure 2'-O-(2-methoxyethyl)-phosphorothioate oligonucleotides.
[So] Source:Chem Commun (Camb);53(3):541-544, 2017 01 03.
[Is] ISSN:1364-548X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Stereochemically-pure 2'-O-(2-methoxyethyl)-phosphorothioate (PS-MOE) oligonucleotides were synthesized from new chiral oxazaphospholidine-containing nucleosides. Thermal stability studies showed that the incorporation of Rp-PS linkages increased RNA-binding affinity. In cells, a full Rp-PS-MOE splice-switching oligonucleotide targeting part of the ferrochelatase gene was more potent than its Sp-PS counterpart, but of similar potency to the stereorandom PS-parent sequence.
[Mh] Termos MeSH primário: Oligonucleotídeos Antissenso/química
Oligonucleotídeos Antissenso/farmacologia
Oligonucleotídeos Fosforotioatos/química
Oligonucleotídeos Fosforotioatos/farmacologia
[Mh] Termos MeSH secundário: Animais
Apolipoproteínas B/genética
Sequência de Bases
Células COS
Cercopithecus aethiops
Ferroquelatase/genética
Seres Humanos
Oligonucleotídeos Antissenso/síntese química
Oligonucleotídeos Fosforotioatos/síntese química
RNA Mensageiro/genética
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Apolipoproteins B); 0 (Oligonucleotides, Antisense); 0 (Phosphorothioate Oligonucleotides); 0 (RNA, Messenger); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161215
[St] Status:MEDLINE
[do] DOI:10.1039/c6cc08473g


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[PMID]:27486032
[Au] Autor:Lobo SA; Videira MA; Pacheco I; Wass MN; Warren MJ; Teixeira M; Matias PM; Romão CV; Saraiva LM
[Ad] Endereço:Instituto de Tecnologia Química e Biológica NOVA, Avenida da República (EAN), Oeiras, 2780-157, Portugal.
[Ti] Título:Desulfovibrio vulgaris CbiK cobaltochelatase: evolution of a haem binding protein orchestrated by the incorporation of two histidine residues.
[So] Source:Environ Microbiol;19(1):106-118, 2017 Jan.
[Is] ISSN:1462-2920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The sulfate-reducing bacteria of the Desulfovibrio genus make three distinct modified tetrapyrroles, haem, sirohaem and adenosylcobamide, where sirohydrochlorin acts as the last common biosynthetic intermediate along the branched tetrapyrrole pathway. Intriguingly, D. vulgaris encodes two sirohydrochlorin chelatases, CbiK and CbiK , that insert cobalt/iron into the tetrapyrrole macrocycle but are thought to be distinctly located in the periplasm and cytoplasm respectively. Fusing GFP onto the C-terminus of CbiK confirmed that the protein is transported to the periplasm. The structure-function relationship of CbiK was studied by constructing eleven site-directed mutants and determining their chelatase activities, oligomeric status and haem binding abilities. Residues His154 and His216 were identified as essential for metal-chelation of sirohydrochlorin. The tetrameric form of the protein is stabilized by Arg54 and Glu76, which form hydrogen bonds between two subunits. His96 is responsible for the binding of two haem groups within the main central cavity of the tetramer. Unexpectedly, CbiK is shown to bind two additional haem groups through interaction with His103. Thus, although still retaining cobaltochelatase activity, the presence of His96 and His103 in CbiK , which are absent from all other known bacterial cobaltochelatases, has evolved CbiK a new function as a haem binding protein permitting it to act as a potential haem chaperone or transporter.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Desulfovibrio vulgaris/enzimologia
Desulfovibrio vulgaris/genética
Heme/análogos & derivados
Liases/genética
Tetrapirróis/metabolismo
Uroporfirinas/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas de Transporte/genética
Desulfovibrio vulgaris/metabolismo
Ferroquelatase/genética
Ferroquelatase/metabolismo
Heme/metabolismo
Hemeproteínas/genética
Histidina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Carrier Proteins); 0 (Hemeproteins); 0 (Tetrapyrroles); 0 (Uroporphyrins); 0 (heme-binding protein); 42VZT0U6YR (Heme); 4QD397987E (Histidine); 52553-42-1 (siroheme); 65207-12-7 (sirohydrochlorin); EC 4.- (Lyases); EC 4.99.1.- (cobaltochelatase); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE
[do] DOI:10.1111/1462-2920.13479


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Fotocópia
[PMID]:27818378
[Au] Autor:Hey D; Ortega-Rodes P; Fan T; Schnurrer F; Brings L; Hedtke B; Grimm B
[Ad] Endereço:Humboldt-University Berlin, Institute of Biology/Plant Physiology, Philippstr.13, Building 12, D-10115 Berlin, Germany.
[Ti] Título:Transgenic Tobacco Lines Expressing Sense or Antisense FERROCHELATASE 1 RNA Show Modified Ferrochelatase Activity in Roots and Provide Experimental Evidence for Dual Localization of Ferrochelatase 1.
[So] Source:Plant Cell Physiol;57(12):2576-2585, 2016 Dec.
[Is] ISSN:1471-9053
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:In plants, two genes encode ferrochelatase (FC), which catalyzes iron chelation into protoporphyrin IX at the final step of heme biosynthesis. FERROCHELATASE1 (FC1) is continuously, but weakly expressed in roots and leaves, while FC2 is dominantly active in leaves. As a continuation of previous studies on the physiological consequences of FC2 inactivation in tobacco, we aimed to assign FC1 function in plant organs. While reduced FC2 expression leads to protoporphyrin IX accumulation in leaves, FC1 down-regulation and overproduction caused reduced and elevated FC activity in root tissue, respectively, but were not associated with changes in macroscopic phenotype, plant development or leaf pigmentation. In contrast to the lower heme content resulting from a deficiency of the dominant FC2 expression in leaves, a reduction of FC1 in roots and leaves does not significantly disturb heme accumulation. The FC1 overexpression was used for an additional approach to re-examine FC activity in mitochondria. Transgenic FC1 protein was immunologically shown to be present in mitochondria. Although matching only a small portion of total cellular FC activity, the mitochondrial FC activity in a FC1 overexpressor line increased 5-fold in comparison with wild-type mitochondria. Thus, it is suggested that FC1 contributes to mitochondrial heme synthesis.
[Mh] Termos MeSH primário: Ferroquelatase/genética
Regulação da Expressão Gênica de Plantas
Protoporfirinas/metabolismo
Tabaco/enzimologia
[Mh] Termos MeSH secundário: Regulação para Baixo
Ferroquelatase/metabolismo
Heme/metabolismo
Mitocôndrias/enzimologia
Especificidade de Órgãos
Fenótipo
Folhas de Planta/enzimologia
Folhas de Planta/genética
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Raízes de Plantas/enzimologia
Raízes de Plantas/genética
Plantas Geneticamente Modificadas
Transporte Proteico
RNA Antissenso/genética
Tabaco/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Proteins); 0 (Protoporphyrins); 0 (RNA, Antisense); 42VZT0U6YR (Heme); C2K325S808 (protoporphyrin IX); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170322
[Lr] Data última revisão:
170322
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161108
[St] Status:MEDLINE



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