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FEBS Journal

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https://www.readbyqxmd.com/read/28921884/structural-characterization-and-functional-analysis-of-cystathionine-%C3%AE-synthase-an-enzyme-involved-in-the-reverse-transsulfuration-pathway-of-bacillus-anthracis
#1
Suneeta Devi, Syed Arif Abdul Rehman, Khaja Faisal Tarique, Samudrala Gourinath
The reverse transsulfuration pathway has been reported to produce cysteine from homocysteine in eukaryotes ranging from protozoans to mammals while bacteria and plants produce cysteine via a de-novo pathway. Interestingly, the bacterium Bacillus anthracis includes enzymes of the reverse transsulfuration pathway viz. cystathionine β-synthase (BaCBS, previously annotated to be an O-acetylserine sulfhydrylase (OASS)) and cystathionine γ-lyase. Here, we report the structure of BaCBS at a resolution of 2.2 Å...
September 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28921866/autophagy-and-cancer-insights-from-mouse-models
#2
REVIEW
Laura Mainz, Mathias T Rosenfeldt
(Macro-)autophagy is an evolutionary conserved "self-digestion program" that serves to maintain cellular metabolism and is implicated in many pathological processes such as cancer. In recent years, an increasing number of studies in murine cancer models have provided a plethora of sometimes conflicting results about the role of autophagy in cancer biology. This review summarises these studies and raises awareness that there are situations in which autophagy blockage might indeed reduce tumor growth, but that sometimes the exact opposite is the case...
September 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28915348/activation-of-factor-xiii-is-accompanied-by-a-change-in-oligomerization-state
#3
Boris A Anokhin, Vilius Stribinskis, William L Dean, Muriel C Maurer
Factor XIII A (FXIIIA) is a member of the transglutaminase enzyme family that cross-links both intra- and extracellular protein substrates. To prevent undesired cross-linking, FXIIIA is expressed as an inactive zymogen and exists intracellularly as an A2 homodimer. In plasma, FXIII A2 is complexed with two protective factor XIII B subunits (A2 B2 ) that dissociate upon activation of the zymogen. Based on limited experimental data, activated FXIII was considered a dimer of two catalytically active A subunits...
September 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28906594/understanding-the-molecular-basis-for-multiple-mitochondrial-dysfunctions-syndrome-1-mmds1-impact-of-a-disease-causing-gly189arg-substitution-on-nfu1
#4
Nathaniel A Wesley, Christine Wachnowsky, Insiya Fidai, J A Cowan
Iron-sulfur (Fe/S) cluster-containing proteins constitute one of the largest protein classes, with highly-varied function. Consequently, the biosynthesis of Fe/S clusters is evolutionarily conserved and mutations in intermediate Fe/S cluster scaffold proteins can cause disease, including multiple mitochondrial dysfunctions syndrome (MMDS). Herein, we have characterized the impact of defects occurring in the MMDS1 disease state that result from a point mutation (p.Gly189Arg) near the active site of NFU1, an iron-sulfur scaffold protein...
September 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28906593/analysis-of-nfu-1-metallocofactor-binding-site-substitutions-impacts-on-iron-sulfur-cluster-coordination-and-protein-structure-and-function
#5
Nathaniel A Wesley, Christine Wachnowsky, Insiya Fidai, J A Cowan
Iron-sulfur (Fe/S) clusters are ancient prosthetic groups found in numerous metalloproteins and are conserved across all kingdoms of life due to their diverse, yet essential functional roles. Genetic mutations to a specific subset of mitochondrial Fe/S cluster delivery proteins are broadly categorized as disease related under multiple mitochondrial dysfunction syndrome (MMDS), with symptoms indicative of a general failure of the metabolic system. Multiple mitochondrial dysfunction syndrome 1 (MMDS1) arises as a result of the missense mutation in NFU1, an Fe/S cluster scaffold protein, which substitutes a glycine near the Fe/S cluster binding pocket to a cysteine (p...
September 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28906061/opposite-effect-of-polymorphic-mutations-on-the-electrostatic-aggregation-of-human-alanine-glyoxylate-aminotransferase-implications-for-the-pathogenesis-of-primary-hyperoxaluria-type-i
#6
Mirco Dindo, Carolina Conter, Barbara Cellini
Protein aggregates formation is the basis of several misfolding diseases, including those displaying loss-of-function pathogenesis. Although aggregation is often attributed to the population of intermediates exposing hydrophobic surfaces, the contribution of electrostatic forces has recently gained attention. Here we combined computational and in vitro studies to investigate the aggregation process of human peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme involved in glyoxylate detoxification...
September 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28898552/a-key-tyrosine-substitution-restricts-nucleotide-hydrolysis-by-the-ectoenzyme-npp5
#7
Alexei Gorelik, Antsa Randriamihaja, Katalin Illes, Bhushan Nagar
The ecto-nucleotide pyrophosphatase / phosphodiesterase (NPP) family of proteins mediates purinergic signaling by degrading extracellular nucleotides, and also participates in phospholipid metabolism. NPP5 (ENPP5) is the least characterized member of this group and its specific role is unknown. This enzyme does not display activity on certain nucleotides and on other typical NPP substrates. In order to gain insights into its function, we determined the crystal structure of human and murine NPP5. Structural comparison with close homologs revealed a key phenylalanine to tyrosine substitution that prevents efficient hydrolysis of nucleotide diphosphates and triphosphates; reversal of this mutation enabled degradation of these molecules...
September 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28898537/stabilizing-an-amyloidogenic-%C3%AE-6-light-chain-variable-domain
#8
Oscar D Luna-Martínez, Alejandra Hernández-Santoyo, Myriam I Villalba-Velázquez, Rosalba Sánchez-Alcalá, D Alejandro Fernández-Velasco, Baltazar Becerril
Light chain amyloidosis is a lethal disease where vital organs are damaged by the fibrillar aggregation of monoclonal light chains. λ6a is an immunoglobulin light chain encoded by the germ line gene segment implicated in this disease. AR is a patient-derived germ line variant with a markedly low thermodynamic stability and prone to form fibrils in vitro in less than an hour. Here, we sought to stabilize this domain by mutating some residues back to the germ line sequence, and the most stabilizing mutations were the single mutant AR-F21I and the double mutant AR-F21/IV104L, both located in the hydrophobic core...
September 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28898525/analyses-of-n-linked-glycans-of-prp-s-c-revealed-predominantly-2-6-linked-sialic-acid-residues
#9
Elizaveta Katorcha, Ilia V Baskakov
Mammalian prions (PrP(S)(c) ) consist of misfolded, conformationally altered, self-replicating states of the sialoglycoprotein called prion protein or PrP(C) . Recent studies revealed that the sialylation status of PrP(S)(c) plays a major role in evading innate immunity and infecting a host. Establishing the type of linkage by which sialic acid residues are attached to galactose is important, as it helps to identify the sialyltransferases responsible for sialylating PrP(C) and outline strategies for manipulating the sialyation status of PrP(S)(c) ...
September 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28892294/nuclease-activity-gives-an-edge-to-host-defense-peptide-piscidin-3-over-piscidin-1-rendering-it-more-effective-against-persisters-and-biofilms
#10
M Daben J Libardo, Ali Adem Bahar, Buyong Ma, Riqiang Fu, Laura E McCormick, Jun Zhao, Scott A McCallum, Ruth Nussinov, Dacheng Ren, Alfredo M Angeles-Boza, Myriam L Cotten
Host defense peptides (HDPs) feature evolution-tested potency against life-threatening pathogens. While piscidin 1 (p1) and piscidin 3 (p3) are homologous and potent fish HDPs, only p1 is strongly membranolytic. Here, we hypothesize that another mechanism imparts p3 strong potency. We demonstrate that the N-termini of both peptides coordinate Cu(2+) and p3-Cu cleaves isolated DNA at a rate on par with free Cu(2+) but significantly faster than p1-Cu. On planktonic bacteria, p1 is more antimicrobial but only p3 features copper-dependent DNA cleavage...
September 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28886238/sirt7-deacetylates-ddb1-and-suppresses-the-activity-of-the-crl4-e3-ligase-complexes
#11
Yan Mo, Ran Lin, Peng Liu, Minjia Tan, Yue Xiong, Kun-Liang Guan, Hai-Xin Yuan
Cullin 4 (CUL4) and small ring finger protein ROC1 assemble to form E3 ubiquitin ligase (CRL4) complexes. CUL4 interacts with WD-40 proteins through the adaptor protein DDB1 to target substrates for ubiquitylation.. Very little is known on how the CUL4 and DDB1 interaction is regulated. Here, we show that DDB1 is acetylated and acetylation promotes DDB1 binding to CUL4. We also identify nucleolar SIRT7 as a major deacetylase that negatively regulates DDB1-CUL4 interaction. Following inhibition of nucleolar function by Actinomycin D (ActD) or 5-Fluorouracil (5-FU) treatment or knocking down Pol I component UBF, SIRT7 is mobilized from the nucleolus to the nucleoplasm and promotes DDB1 deacetylation, leading to decreased DDB1-CUL4 association and CRL4 activity...
September 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28886229/structural-insight-into-a-partially-unfolded-state-preceding-aggregation-in-an-intracellular-lipid-binding-protein
#12
Gergő Horváth, László Biczók, Zsuzsa Majer, Mihály Kovács, András Micsonai, József Kardos, Orsolya Toke
Human ileal bile acid-binding protein (I-BABP) has a key role in the intracellular transport and metabolic targeting of bile salts. Similarly to other members of the family of intracellular lipid binding proteins (iLBPs), disorder-order transitions and local unfolding processes are thought to mediate ligand entry and release in human I-BABP. To gain insight into the stability of various protein regions, the temperature response of human I-BABP was investigated using NMR, CD, and fluorescence spectroscopy, as well as molecular dynamics (MD) simulations...
September 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28881496/xk-related-protein-8-regulates-myoblast-differentiation-and-survival
#13
Go-Woon Kim, Gi-Hoon Nam, In-San Kim, Seung-Yoon Park
Xk-related protein 8 (Xkr8) is a scramblase and responsible for PS exposure on the cell surface in a caspase-dependent manner. Although PS exposure is found to be important for myotube formation during myoblast differentiation, the role of Xkr8 during myogenesis has not been elucidated. Here we show that Xkr8 contributes to myoblast differentiation. Xkr8 overexpression induced the formation of large myotubes during early differentiation, but this phenotype was not related to caspase-dependent cleavage of Xkr8...
September 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28881486/how-usp18-deals-with-isg15-modified-proteins-structural-basis-for-the-specificity-of-the-protease
#14
REVIEW
Anja Basters, Klaus-Peter Knobeloch, Günter Fritz
The Ubiquitin-specific protease 18 (USP18) has two major functions: (i) it is a highly specific protease that cleaves the ubiquitin-like modifier ISG15 (interferon stimulated gene 15 kDa) from proteins, and (ii) independent from its enzymatic activity USP18 interacts with the type I interferon receptor and shuts off downstream signaling. The structures of USP18 and a USP18-ISG15 complex revealed the molecular basis of the unique specificity of the protease and might shed some light into its interaction with the interferon receptor...
September 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28881427/active-site-geometry-of-a-novel-aminopropyltransferase-for-biosynthesis-of-hyperthermophile-specific-branched-chain-polyamine
#15
Ryota Hidese, Ka Man Tse, Seigo Kimura, Eiichi Mizohata, Junso Fujita, Yuhei Horai, Naoki Umezawa, Tsunehiko Higuchi, Masaru Niitsu, Tairo Oshima, Tadayuki Imanaka, Tsuyoshi Inoue, Shinsuke Fujiwara
Branched-chain polyamines are found exclusively in thermophilic bacteria and Euryarchaeota and play essential roles in survival at high temperatures. In the present study, kinetic analyses of a branched-chain polyamine synthase from the hyperthermophilic archaeon Thermococcus kodakarensis (Tk-BpsA) were conducted, showing that N(4) -bis(aminopropyl)spermidine was produced by sequential additions of decarboxylated S-adenosyladenosine (dcSAM) aminopropyl groups to spermidine, through bifunctional catalytic action...
September 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28869789/subtle-changes-in-the-active-site-architecture-untangled-overlapping-substrate-ranges-and-mechanistic-differences-of-two-reductive-dehalogenases
#16
Cindy Kunze, Gabriele Diekert, Torsten Schubert
Reductive dehalogenases (RDases) of organohalide-respiring bacteria are cobamide-containing iron-sulfur proteins that catalyze different reductive dehalogenation reactions. Here, we report a functional analysis of two recombinant RDases, the tetrachloroethene (PCE) reductive dehalogenase (PceA) of Desulfitobacterium hafniense Y51 and the 1,2-dichloroethane (DCA) reductive dehalogenase (DcaA) of Desulfitobacterium dichloroeliminans DCA1. Both enzymes share 88% protein sequence identity, but appeared to have divergent mechanisms...
September 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28857485/non-alcoholic-fatty-liver-disease-promotes-hepatocellular-carcinoma-through-direct-and-indirect-effects-on-hepatocytes
#17
REVIEW
Chi Ma, Qianfei Zhang, Tim F Greten
Hepatocellular carcinoma (HCC) is the sixth most frequent neoplasm and the second leading cause of cancer-related deaths worldwide. Non-alcoholic fatty liver disease (NAFLD), a common disorder in obese people, has been identified as an important risk factor for HCC. Following the increasing prevalence of obesity, it is expected that the contribution of NAFLD to HCC's incidence worldwide will grow. Recently, a number of studies have been published, which help us better understand cellular and molecular mechanisms of how NAFLD promotes hepatocarcinogensis...
August 31, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28857479/crystal-structure-of-a-lipase-from-streptomyces-sp-strain-w007-implications-for-thermostability-and-regiospecificity
#18
Zexin Zhao, Shulin Hou, Dongming Lan, Xiumei Wang, Jinsong Liu, Faez Iqbal Khan, Yonghua Wang
MAS1 from marine Streptomyces sp. strain W007 belongs to the bacterial lipase I.7 subfamily, and is characterized as a thermostable and non-regiospecific lipase. To shed light on the catalytic mechanism of MAS1, we determined its crystal structure with closed conformation in two crystal forms at 2.3-Å resolution. MAS1 adopts the canonical α/β hydrolase core fold with its catalytic triad being formed by S109, D200 and H232. Structural analysis and biochemical assays revealed that disulfide bonds and salt bridges play a vital role in the thermostability of MAS1...
August 31, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28857430/non-resolving-macrophage-mediated-inflammation-in-malignancy
#19
REVIEW
Peter J Murray
Tumors are populated with different cells of the immune system, each of which has the potential for pro- or anti-tumor functions. Macrophages are the numerically dominant type of myeloid cell in cancer and are suspected of having predominantly pro-tumor functions. Key questions in cancer research concern the relationships between macrophages and anatomically different kinds of cancers, what specific properties of macrophages are involved in pro-tumor functions and whether either macrophage numbers or functions can be modulated to enhance existing cancer therapies, for example, by reducing the immunosuppressive milieu such that anti-tumor T cells can provoke anti-tumor immunity...
August 31, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28837266/covalent-dimerization-of-interleukin-like-epithelial-to-mesenchymal-transition-emt-inducer-ilei-facilitates-emt-invasion-and-late-aspects-of-metastasis
#20
Maria Kral, Christoph Klimek, Betül Kutay, Gerald Timelthaler, Thomas Lendl, Benjamin Neuditschko, Christopher Gerner, Maria Sibilia, Agnes Csiszar
The interleukin-like epithelial-to-mesenchymal transition (EMT) inducer (ILEI)/FAM3C is a member of the highly homologous FAM3 family and is essential for EMT and metastasis formation. It is upregulated in several cancers, and its altered subcellular localization strongly correlates with poor survival. However, the mechanism of ILEI action, including the structural requirements for ILEI activity, remains elusive. Here, we show that ILEI formed both monomers and covalent dimers in cancer cell lines and in tumors...
August 24, 2017: FEBS Journal
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