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  1 / 2074 MEDLINE  
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[PMID]:29362370
[Au] Autor:Kathayat RS; Cao Y; Elvira PD; Sandoz PA; Zaballa ME; Springer MZ; Drake LE; Macleod KF; van der Goot FG; Dickinson BC
[Ad] Endereço:Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
[Ti] Título:Active and dynamic mitochondrial S-depalmitoylation revealed by targeted fluorescent probes.
[So] Source:Nat Commun;9(1):334, 2018 01 23.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The reversible modification of cysteine residues by thioester formation with palmitate (S-palmitoylation) is an abundant lipid post-translational modification (PTM) in mammalian systems. S-palmitoylation has been observed on mitochondrial proteins, providing an intriguing potential connection between metabolic lipids and mitochondrial regulation. However, it is unknown whether and/or how mitochondrial S-palmitoylation is regulated. Here we report the development of mitoDPPs, targeted fluorescent probes that measure the activity levels of "erasers" of S-palmitoylation, acyl-protein thioesterases (APTs), within mitochondria of live cells. Using mitoDPPs, we discover active S-depalmitoylation in mitochondria, in part mediated by APT1, an S-depalmitoylase previously thought to reside in the cytosol and on the Golgi apparatus. We also find that perturbation of long-chain acyl-CoA cytoplasm and mitochondrial regulatory proteins, respectively, results in selective responses from cytosolic and mitochondrial S-depalmitoylases. Altogether, this work reveals that mitochondrial S-palmitoylation is actively regulated by "eraser" enzymes that respond to alterations in mitochondrial lipid homeostasis.
[Mh] Termos MeSH primário: Corantes Fluorescentes/metabolismo
Mitocôndrias/metabolismo
Dinâmica Mitocondrial
Tioléster Hidrolases/metabolismo
[Mh] Termos MeSH secundário: Células A549
Acil Coenzima A/metabolismo
Células HEK293
Células HeLa
Seres Humanos
Cinética
Lipoilação
Células MCF-7
Microscopia Confocal
Interferência de RNA
Tioléster Hidrolases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acyl Coenzyme A); 0 (Fluorescent Dyes); EC 3.1.2.- (LYPLA1 protein, human); EC 3.1.2.- (Thiolester Hydrolases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02655-1


  2 / 2074 MEDLINE  
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[PMID]:29364904
[Au] Autor:Garland M; Schulze CJ; Foe IT; van der Linden WA; Child MA; Bogyo M
[Ad] Endereço:Cancer Biology Program, Stanford University School of Medicine, Stanford, California, United States of America.
[Ti] Título:Development of an activity-based probe for acyl-protein thioesterases.
[So] Source:PLoS One;13(1):e0190255, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein palmitoylation is a dynamic post-translational modification (PTM) important for cellular functions such as protein stability, trafficking, localization, and protein-protein interactions. S-palmitoylation occurs via the addition of palmitate to cysteine residues via a thioester linkage, catalyzed by palmitoyl acyl transferases (PATs), with removal of the palmitate catalyzed by acyl protein thioesterases (APTs) and palmitoyl-protein thioesterases (PPTs). Tools that target the regulators of palmitoylation-PATs, APTs and PPTs-will improve understanding of this essential PTM. Here, we describe the synthesis and application of a cell-permeable activity-based probe (ABP) that targets APTs in intact mammalian cells and the parasite Toxoplasma gondii. Using a focused library of substituted chloroisocoumarins, we identified a probe scaffold with nanomolar affinity for human APTs (HsAPT1 and HsAPT2) and synthesized a fluorescent ABP, JCP174-BODIPY TMR (JCP174-BT). We use JCP174-BT to profile HsAPT activity in situ in mammalian cells, to detect an APT in T. gondii (TgPPT1). We show discordance between HsAPT activity levels and total protein concentration in some cell lines, indicating that total protein levels may not be representative of APT activity in complex systems, highlighting the utility of this probe.
[Mh] Termos MeSH primário: Sondas Moleculares/metabolismo
[Mh] Termos MeSH secundário: Animais
Mamíferos
Processamento de Proteína Pós-Traducional
Tioléster Hidrolases
Toxoplasma/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Molecular Probes); EC 3.1.2.- (Thiolester Hydrolases); EC 3.1.2.22 (palmitoyl-protein thioesterase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190255


  3 / 2074 MEDLINE  
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[PMID]:29293652
[Au] Autor:Stockum A; Snijders AP; Maertens GN
[Ad] Endereço:Imperial College London, Department of Medicine, Division of Infectious Diseases, Norfolk Place, London, United Kingdom.
[Ti] Título:USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation.
[So] Source:PLoS One;13(1):e0190513, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Correct segregation of the mitotic chromosomes into daughter cells is a highly regulated process critical to safeguard genome stability. During M phase the spindle assembly checkpoint (SAC) ensures that all kinetochores are correctly attached before its inactivation allows progression into anaphase. Upon SAC inactivation, the anaphase promoting complex/cyclosome (APC/C) E3 ligase ubiquitinates and targets cyclin B and securin for proteasomal degradation. Here, we describe the identification of Ribonucleic Acid Export protein 1 (RAE1), a protein previously shown to be involved in SAC regulation and bipolar spindle formation, as a novel substrate of the deubiquitinating enzyme (DUB) Ubiquitin Specific Protease 11 (USP11). Lentiviral knock-down of USP11 or RAE1 in U2OS cells drastically reduces cell proliferation and increases multipolar spindle formation. We show that USP11 is associated with the mitotic spindle, does not regulate SAC inactivation, but controls ubiquitination of RAE1 at the mitotic spindle, hereby functionally modulating its interaction with Nuclear Mitotic Apparatus protein (NuMA).
[Mh] Termos MeSH primário: Proteínas Associadas à Matriz Nuclear/metabolismo
Proteínas de Transporte Nucleocitoplasmático/metabolismo
Fuso Acromático
Tioléster Hidrolases/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Proliferação Celular
Técnicas de Silenciamento de Genes
Células HEK293
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Ligação Proteica
Especificidade por Substrato
Tioléster Hidrolases/genética
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (Nuclear Matrix-Associated Proteins); 0 (Nucleocytoplasmic Transport Proteins); 0 (RAE1 protein, human); 0 (SPRY3 protein, human); EC 3.1.2.- (Thiolester Hydrolases); EC 3.1.2.15 (USP11 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190513


  4 / 2074 MEDLINE  
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[PMID]:28945249
[Au] Autor:Gersch M; Gladkova C; Schubert AF; Michel MA; Maslen S; Komander D
[Ad] Endereço:Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
[Ti] Título:Mechanism and regulation of the Lys6-selective deubiquitinase USP30.
[So] Source:Nat Struct Mol Biol;24(11):920-930, 2017 Nov.
[Is] ISSN:1545-9985
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Damaged mitochondria undergo mitophagy, a specialized form of autophagy that is initiated by the protein kinase PINK1 and the ubiquitin E3 ligase Parkin. Ubiquitin-specific protease USP30 antagonizes Parkin-mediated ubiquitination events on mitochondria and is a key negative regulator of mitophagy. Parkin and USP30 both show a preference for assembly or disassembly, respectively, of Lys6-linked polyubiquitin, a chain type that has not been well studied. Here we report crystal structures of human USP30 bound to monoubiquitin and Lys6-linked diubiquitin, which explain how USP30 achieves Lys6-linkage preference through unique ubiquitin binding interfaces. We assess the interplay between USP30, PINK1 and Parkin and show that distally phosphorylated ubiquitin chains impair USP30 activity. Lys6-linkage-specific affimers identify numerous mitochondrial substrates for this modification, and we show that USP30 regulates Lys6-polyubiquitinated TOM20. Our work provides insights into the architecture, activity and regulation of USP30, which will aid drug design against this and related enzymes.
[Mh] Termos MeSH primário: Enzimas Desubiquitinantes/química
Enzimas Desubiquitinantes/metabolismo
Proteínas Mitocondriais/química
Proteínas Mitocondriais/metabolismo
Tioléster Hidrolases/química
Tioléster Hidrolases/metabolismo
Ubiquitina/química
Ubiquitina/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Ligação Proteica
Proteínas Quinases/metabolismo
Especificidade por Substrato
Ubiquitina-Proteína Ligases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 0 (Ubiquitin); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.3.2.27 (parkin protein); EC 2.7.- (Protein Kinases); EC 2.7.11.1 (PTEN-induced putative kinase); EC 3.1.2.- (Thiolester Hydrolases); EC 3.1.2.15 (Usp30 protein, human); EC 3.4.19.12 (Deubiquitinating Enzymes)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE
[do] DOI:10.1038/nsmb.3475


  5 / 2074 MEDLINE  
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[PMID]:28634076
[Au] Autor:Xiong H; Li B; He J; Zeng Y; Zhang Y; He F
[Ad] Endereço:Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
[Ti] Título:lncRNA HULC promotes the growth of hepatocellular carcinoma cells via stabilizing COX-2 protein.
[So] Source:Biochem Biophys Res Commun;490(3):693-699, 2017 Aug 26.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Highly upregulated in liver cancer (HULC), a lncRNA overexpressed in hepatocellular carcinoma (HCC), has been demonstrated to be involved in the carcinogenesis and progression of HCC. However, the mechanisms of HULC promoting the abnormal growth of HCC cells are still not well elucidated. In the present study, we for the first time demonstrated that HULC promoted the growth of HCC cells through elevating COX-2 protein. Moreover, the study of the corresponding mechanism by which HULC upregulated COX-2 showed that HULC enhanced the level of ubiquitin-specific peptidase 22 (USP22), which decreased ubiquitin-mediated degradation of COX-2 protein by removing the conjugated polyubiquitin chains from COX-2 and finally stabilized COX2 protein. In addition, knockdown of USP22 or COX-2 attenuated HULC-mediated abnormal growth of HCC cells. In conclusion, our results demonstrated that "USP22/COX-2" axis played an important role in HULC promoting growth of HCC cells. The identification of this novel pathway may pave a road for developing new potential anti-HCC strategies.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/patologia
Ciclo-Oxigenase 2/metabolismo
Regulação Neoplásica da Expressão Gênica
Neoplasias Hepáticas/patologia
Fígado/patologia
RNA Longo não Codificante/genética
Tioléster Hidrolases/genética
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/metabolismo
Linhagem Celular Tumoral
Seres Humanos
Fígado/metabolismo
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/metabolismo
Estabilidade Proteica
Proteólise
RNA Longo não Codificante/metabolismo
Tioléster Hidrolases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HULC long non-coding RNA, human); 0 (RNA, Long Noncoding); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (PTGS2 protein, human); EC 3.1.2.- (Thiolester Hydrolases); EC 3.1.2.15 (Usp22 protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170622
[St] Status:MEDLINE


  6 / 2074 MEDLINE  
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[PMID]:28607105
[Au] Autor:Franklin MP; Sathyanarayan A; Mashek DG
[Ad] Endereço:Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN.
[Ti] Título:Acyl-CoA Thioesterase 1 (ACOT1) Regulates PPARα to Couple Fatty Acid Flux With Oxidative Capacity During Fasting.
[So] Source:Diabetes;66(8):2112-2123, 2017 Aug.
[Is] ISSN:1939-327X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatic acyl-CoA thioesterase 1 (ACOT1) catalyzes the conversion of acyl-CoAs to fatty acids (FAs) and CoA. We sought to determine the role of ACOT1 in hepatic lipid metabolism in C57Bl/6J male mice 1 week after adenovirus-mediated knockdown. knockdown reduced liver triglyceride (TG) as a result of enhanced TG hydrolysis and subsequent FA oxidation. In vitro experiments demonstrated that knockdown led to greater TG turnover and FA oxidation, suggesting that ACOT1 is important for controlling the rate of FA oxidation. Despite increased FA oxidation, knockdown reduced the expression of peroxisome proliferator-activated receptor α (PPARα) target genes, whereas overexpression increased PPARα reporter activity, suggesting ACOT1 regulates PPARα by producing FA ligands. Moreover, ACOT1 exhibited partial nuclear localization during fasting and cAMP/cAMP-dependent protein kinase signaling, suggesting local regulation of PPARα. As a consequence of increased FA oxidation and reduced PPARα activity, knockdown enhanced hepatic oxidative stress and inflammation. The effects of knockdown on PPARα activity, oxidative stress, and inflammation were rescued by supplementation with Wy-14643, a synthetic PPARα ligand. We demonstrate through these results that ACOT1 regulates fasting hepatic FA metabolism by balancing oxidative flux and capacity.
[Mh] Termos MeSH primário: Jejum/fisiologia
Ácidos Graxos/metabolismo
Acoplamento Oxidativo
PPAR alfa/metabolismo
Tioléster Hidrolases/fisiologia
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Fígado/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Estresse Oxidativo/efeitos dos fármacos
Estresse Oxidativo/fisiologia
Pirimidinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Fatty Acids); 0 (PPAR alpha); 0 (Pyrimidines); 86C4MRT55A (pirinixic acid); EC 3.1.2.- (Thiolester Hydrolases); EC 3.1.2.14 (CTE-1 protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.2337/db16-1519


  7 / 2074 MEDLINE  
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[PMID]:28604753
[Au] Autor:Spolverini A; Fuchs G; Bublik DR; Oren M
[Ad] Endereço:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
[Ti] Título:let-7b and let-7c microRNAs promote histone H2B ubiquitylation and inhibit cell migration by targeting multiple components of the H2B deubiquitylation machinery.
[So] Source:Oncogene;36(42):5819-5828, 2017 Oct 19.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Monoubiquitylation of histone H2B (H2Bub1) is catalyzed mainly by the RNF20/RNF40 complex and erased by multiple deubiquitylating enzymes (DUBs). H2Bub1 influences many aspects of chromatin function, including transcription regulation and DNA repair. Cancer cells often display reduced levels of H2Bub1, and this reduction may contribute to cancer progression. The let-7 family of microRNAs (miRNAs) comprises multiple members with reported tumor-suppressive features, whose expression is frequently downregulated in cancer. We now report that let-7b and let-7c can positively regulate cellular H2Bub1 levels. Overexpression of let-7b and let-7c in a variety of non-transformed and cancer-derived cell lines results in H2Bub1 elevation. The positive effect of let-7b and let-7c on H2Bub1 levels is achieved through targeting of multiple mRNAs, coding for distinct components of the H2B deubiquitylation machinery. Specifically, let-7b and let-7c bind directly and inhibit the mRNAs encoding the DUBs USP42 and USP44, and also the mRNA encoding the adapter protein ATXN7L3, which is part of the DUB module of the SAGA complex. RNF20 knockdown (KD) strongly reduces H2Bub1 levels and increases the migration of non-transformed mammary epithelial cells and breast cancer-derived cells. Remarkably, overexpression of let-7b, which partly counteracts the effect of RNF20 KD on H2Bub1 levels, also reverses the pro-migratory effect of RNF20 KD. Likewise, ATXN7L3 KD also increases H2Bub1 levels and reduces cell migration, and this anti-migratory effect is abolished by simultaneous KD of RNF20. Together, our findings uncover a novel function of let-7 miRNAs as regulators of H2B ubiquitylation, suggesting an additional mechanism whereby these miRNAs can exert their tumor-suppressive effects.
[Mh] Termos MeSH primário: Neoplasias da Mama/patologia
Movimento Celular/fisiologia
Histonas/metabolismo
Neoplasias Pulmonares/patologia
MicroRNAs/metabolismo
[Mh] Termos MeSH secundário: Neoplasias da Mama/genética
Neoplasias da Mama/metabolismo
Linhagem Celular Tumoral
Proliferação Celular
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/metabolismo
MicroRNAs/genética
Transdução de Sinais
Tioléster Hidrolases/metabolismo
Fatores de Transcrição/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
Proteases Específicas de Ubiquitina/metabolismo
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATXN7L3 protein, human); 0 (Histones); 0 (MicroRNAs); 0 (Transcription Factors); 0 (mirnlet7 microRNA, human); EC 2.3.2.27 (RNF20 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 3.1.2.- (Thiolester Hydrolases); EC 3.1.2.15 (USP42 protein, human); EC 3.4.19.12 (USP44 protein, human); EC 3.4.19.12 (Ubiquitin-Specific Proteases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.187


  8 / 2074 MEDLINE  
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[PMID]:28550989
[Au] Autor:Wang M; Nie K; Cao H; Xu H; Fang Y; Tan T; Baeyens J; Liu L
[Ad] Endereço:Beijing Bioprocess Key Laboratory, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China.
[Ti] Título:Biosynthesis of medium chain length alkanes for bio-aviation fuel by metabolic engineered Escherichia coli.
[So] Source:Bioresour Technol;239:542-545, 2017 Sep.
[Is] ISSN:1873-2976
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The aim of this work was to study the synthesis of medium-chain length alkanes (MCLA), as bio-aviation product. To control the chain length of alkanes and increase the production of MCLA, Escherichia coli cells were engineered by incorporating (i) a chain length specific thioesterase from Umbellularia californica (UC), (ii) a plant origin acyl carrier protein (ACP) gene and (iii) the whole fatty acid synthesis system (FASs) from Jatropha curcas (JC). The genetic combination was designed to control the product spectrum towards optimum MCLA. Decanoic, lauric and myristic acid were produced at concentrations of 0.011, 0.093 and 1.657mg/g, respectively. The concentration of final products nonane, undecane and tridecane were 0.00062mg/g, 0.0052mg/g, and 0.249mg/g respectively. Thioesterase from UC controlled the fatty acid chain length in a range of 10-14 carbons and the ACP gene with whole FASs from JC significantly increased the production of MCLA.
[Mh] Termos MeSH primário: Alcanos
Biocombustíveis
[Mh] Termos MeSH secundário: Aviação
Escherichia coli
Ácidos Graxos
Tioléster Hidrolases
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkanes); 0 (Biofuels); 0 (Fatty Acids); EC 3.1.2.- (Thiolester Hydrolases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170529
[St] Status:MEDLINE


  9 / 2074 MEDLINE  
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[PMID]:28522606
[Au] Autor:Chisuga T; Miyanaga A; Kudo F; Eguchi T
[Ad] Endereço:From the Department of Chemistry and Materials Science and.
[Ti] Título:Structural analysis of the dual-function thioesterase SAV606 unravels the mechanism of Michael addition of glycine to an α,ß-unsaturated thioester.
[So] Source:J Biol Chem;292(26):10926-10937, 2017 Jun 30.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Thioesterases catalyze hydrolysis of acyl thioesters to release carboxylic acid or macrocyclization to produce the corresponding macrocycle in the biosynthesis of fatty acids, polyketides, or nonribosomal peptides. Recently, we reported that the thioesterase CmiS1 from sp. MJ635-86F5 catalyzes the Michael addition of glycine to an α,ß-unsaturated fatty acyl thioester followed by thioester hydrolysis in the biosynthesis of the macrolactam antibiotic cremimycin. However, the molecular mechanisms of CmiS1-catalyzed reactions are unclear. Here, we report on the functional and structural characterization of the CmiS1 homolog SAV606 from MA-4680. analysis indicated that SAV606 catalyzes the Michael addition of glycine to crotonic acid thioester and subsequent hydrolysis yielding ( )- -carboxymethyl-3-aminobutyric acid. We also determined the crystal structures of SAV606 both in ligand-free form at 2.4 Å resolution and in complex with ( )- -carboxymethyl-3-aminobutyric acid at 2.0 Å resolution. We found that SAV606 adopts an α/ß hotdog fold and has an active site at the dimeric interface. Examining the complexed structure, we noted that the substrate-binding loop comprising Tyr-53-Asn-61 recognizes the glycine moiety of ( )- -carboxymethyl-3-aminobutyric acid. Moreover, we found that SAV606 does not contain an acidic residue at the active site, which is distinct from canonical hotdog thioesterases. Site-directed mutagenesis experiments revealed that His-59 plays a crucial role in both the Michael addition and hydrolysis via a water molecule. These results allow us to propose the reaction mechanism of the SAV606-catalyzed Michael addition and thioester hydrolysis and provide new insight into the multiple functions of a thioesterase family enzyme.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Streptomyces/enzimologia
Tioléster Hidrolases/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Catálise
Glicina/química
Glicina/metabolismo
Mutagênese Sítio-Dirigida
Estrutura Secundária de Proteína
Streptomyces/genética
Sulfetos/química
Sulfetos/metabolismo
Tioléster Hidrolases/genética
Tioléster Hidrolases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Sulfides); EC 3.1.2.- (Thiolester Hydrolases); TE7660XO1C (Glycine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.792549


  10 / 2074 MEDLINE  
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[PMID]:28409415
[Au] Autor:Mahmud JA; Hasanuzzaman M; Nahar K; Rahman A; Hossain MS; Fujita M
[Ad] Endereço:Laboratory of Plant Stress Responses, Department of Applied Biological Science, Faculty of Agriculture, Kagawa University, Miki-cho, Kita-gun, Kagawa, 761-0795, Japan.
[Ti] Título:γ-aminobutyric acid (GABA) confers chromium stress tolerance in Brassica juncea L. by modulating the antioxidant defense and glyoxalase systems.
[So] Source:Ecotoxicology;26(5):675-690, 2017 Jul.
[Is] ISSN:1573-3017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromium (Cr) toxicity is hazardous to the seed germination, growth, and development of plants. γ-aminobutyric acid (GABA) is a non-protein amino acid and is involved in stress tolerance in plants. To investigate the effects of GABA in alleviating Cr toxicity, we treated eight-d-old mustard (Brassica juncea L.) seedlings with Cr (0.15 and 0.3 mM K CrO , 5 days) alone and in combination with GABA (125 µM) in a semi-hydroponic medium. The roots and shoots of the seedlings accumulated Cr in a dose-dependent manner, which led to an increase in oxidative damage [lipid peroxidation; hydrogen peroxide (H O ) content; superoxide (O ) generation; lipoxygenase (LOX) activity], methylglyoxal (MG) content, and disrupted antioxidant defense and glyoxalase systems. Chromium stress also reduced growth, leaf relative water content (RWC), and chlorophyll (chl) content but increased phytochelatin (PC) and proline (Pro) content. Furthermore, supplementing the Cr-treated seedlings with GABA reduced Cr uptake and upregulated the non-enzymatic antioxidants (ascorbate, AsA; glutathione, GSH) and the activities of the enzymatic antioxidants including ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), glyoxalase I (Gly I), and glyoxalase II (Gly II), and finally reduced oxidative damage. Adding GABA also increased leaf RWC and chl content, decreased Pro and PC content, and restored plant growth. These findings shed light on the effect of GABA in improving the physiological mechanisms of mustard seedlings in response to Cr stress.
[Mh] Termos MeSH primário: Adaptação Fisiológica/fisiologia
Cromo/toxicidade
Mostardeira/fisiologia
Poluentes do Solo/toxicidade
Ácido gama-Aminobutírico/metabolismo
[Mh] Termos MeSH secundário: Antioxidantes/metabolismo
Ascorbato Peroxidases/metabolismo
Ácido Ascórbico/metabolismo
Catalase/metabolismo
Clorofila/metabolismo
Glutationa/metabolismo
Glutationa Peroxidase/metabolismo
Glutationa Redutase/metabolismo
Peróxido de Hidrogênio/metabolismo
Lactoilglutationa Liase/metabolismo
Fitoquelatinas/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Superóxido Dismutase/metabolismo
Tioléster Hidrolases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Reactive Oxygen Species); 0 (Soil Pollutants); 0R0008Q3JB (Chromium); 1406-65-1 (Chlorophyll); 56-12-2 (gamma-Aminobutyric Acid); 98726-08-0 (Phytochelatins); BBX060AN9V (Hydrogen Peroxide); EC 1.11.1.11 (Ascorbate Peroxidases); EC 1.11.1.6 (Catalase); EC 1.11.1.9 (Glutathione Peroxidase); EC 1.15.1.1 (Superoxide Dismutase); EC 1.8.1.7 (Glutathione Reductase); EC 3.1.2.- (Thiolester Hydrolases); EC 3.1.2.6 (hydroxyacylglutathione hydrolase); EC 4.4.1.5 (Lactoylglutathione Lyase); GAN16C9B8O (Glutathione); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170415
[St] Status:MEDLINE
[do] DOI:10.1007/s10646-017-1800-9



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