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https://www.readbyqxmd.com/read/28383907/substrate-dependent-cleavage-site-selection-by-unconventional-radical-sam-enzymes-in-diphthamide-biosynthesis
#1
Min Dong, Masaki Horitani, Boris Dzikovski, Jack H Freed, Steven Ealick, Brian M Hoffman, Hening Lin
S-adenosylmethionine (SAM) has a sulfonium ion with three distinct C-S bonds. Conventional radical SAM enzymes use a [4Fe-4S] cluster to homolytically cleave the C5',adenosine-S bond of SAM to generate a 5'-deoxyadenosyl radical, which catalyz-es various downstream chemical reactions. Radical SAM en-zymes involved in diphthamide biosynthesis, such as Pyrococ-cus horikoshii Dph2 (PhDph2) and yeast Dph1-Dph2 instead cleave the Cγ,Met-S bond of methionine to generate the 3-amino-3-carboxylpropyl radical. We here show that radical SAM enzymes can be tuned to cleave the third C-S bond to the sulfonium sulfur by changing the structure of SAM...
April 6, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28366513/cost-of-new-technologies-in-prostate-cancer-treatment-systematic-review-of-costs-and-cost-effectiveness-of-robotic-assisted-laparoscopic-prostatectomy-intensity-modulated-radiotherapy-and-proton-beam-therapy
#2
REVIEW
Florian Rudolf Schroeck, Bruce L Jacobs, Sam B Bhayani, Paul L Nguyen, David Penson, Jim Hu
CONTEXT: Some of the high costs of robot-assisted radical prostatectomy (RARP), intensity-modulated radiotherapy (IMRT), and proton beam therapy may be offset by better outcomes or less resource use during the treatment episode. OBJECTIVE: To systematically review the literature to identify the key economic trade-offs implicit in a particular treatment choice for prostate cancer. EVIDENCE ACQUISITION: We systematically reviewed the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement and protocol...
March 30, 2017: European Urology
https://www.readbyqxmd.com/read/28361051/on-the-role-of-additional-4fe-4s-clusters-with-a-free-coordination-site-in-radical-sam-enzymes
#3
REVIEW
Etienne Mulliez, Victor Duarte, Simon Arragain, Marc Fontecave, Mohamed Atta
The canonical CysXXXCysXXCys motif is the hallmark of the Radical-SAM superfamily. This motif is responsible for the ligation of a [4Fe-4S] cluster containing a free coordination site available for SAM binding. The five enzymes MoaA, TYW1, MiaB, RimO and LipA contain in addition a second [4Fe-4S] cluster itself bound to three other cysteines and thus also displaying a potentially free coordination site. This review article summarizes recent important achievements obtained on these five enzymes with the main focus to delineate the role of this additional [4Fe-4S] cluster in catalysis...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28346939/a-b12-dependent-radical-sam-enzyme-involved-in-oxetanocin-a-biosynthesis
#4
Jennifer Bridwell-Rabb, Aoshu Zhong, He G Sun, Catherine L Drennan, Hung-Wen Liu
Oxetanocin A (OXT-A) is a potent antitumour, antiviral and antibacterial compound. Biosynthesis of OXT-A has been linked to a plasmid-borne Bacillus megaterium gene cluster that contains four genes: oxsA, oxsB, oxrA and oxrB. Here we show that both the oxsA and oxsB genes are required for the production of OXT-A. Biochemical analysis of the encoded proteins, a cobalamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohydrolase, OxsA, reveals that OXT-A is derived from a 2'-deoxyadenosine phosphate in an OxsB-catalysed ring contraction reaction initiated by hydrogen atom abstraction from C2'...
April 20, 2017: Nature
https://www.readbyqxmd.com/read/28338506/a-preliminary-report-radical-surgery-and-stem-cell-transplantation-for-the-treatment-of-patients-with-pancreatic-cancer
#5
Brigitta Omazic, Burcu Ayoglu, Matthias Löhr, Ralf Segersvärd, Caroline Verbeke, Isabelle Magalhaes, Zuzana Potacova, Jonas Mattsson, Alexei Terman, Sam Ghazi, Nils Albiin, Nikolaos Kartalis, Peter Nilsson, Thomas Poiret, Liu Zhenjiang, Rainer Heuchel, Jochen M Schwenk, Johan Permert, Markus J Maeurer, Olle Ringden
We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28301141/reconstitution-and-substrate-specificity-of-the-radical-s-adenosyl-methionine-thiazole-c-methyltransferase-in-thiomuracin-biosynthesis
#6
Nilkamal Mahanta, Zhengan Zhang, Graham A Hudson, Wilfred A van der Donk, Douglas A Mitchell
Thiomuracin is a thiopeptide antibiotic with potent activity toward Gram-positive drug-resistant bacteria. Thiomuracin is biosynthesized from a precursor peptide, TbtA, by a complex array of posttranslational modifications. One of several intriguing transformations is the C-methylation of thiazole, occurring at an unactivated sp(2) carbon. Herein, we report the in vitro reconstitution of TbtI, the responsible radical S-adenosyl-methionine (rSAM) C-methyltransferase, which catalyzes the formation of 5-methylthiazole at a single site...
March 29, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28294069/wallet-neuritis-an-example-of-peripheral-sensitization
#7
Md Abu Bakar Siddiq, Israt Jahan, Sam Masihuzzaman
BACKGROUND: Wallet neuritis is an example of extra-spinal tunnel neuropathy concerning sciatic nerve. Its clinical appearance often gets confused with sciatica of lumbar spine origin. Wallet-induced chronic sciatic nerve constriction produces gluteal and ipsilateral lower extremity pain, tingling, and burning sensation. It was Lutz, first describing credit-card wallet sciatica in an Attorney, surfaced on Journal of American Medical Association (JAMA), 1978; however, the condition has not been well-studied in various other occupations...
March 9, 2017: Current Rheumatology Reviews
https://www.readbyqxmd.com/read/28282126/tuning-the-rectification-ratio-by-changing-the-electronic-nature-open-shell-and-closed-shell-in-donor-acceptor-self-assembled-monolayers
#8
Manuel Souto, Li Yuan, Dayana C Morales, Li Jiang, Imma Ratera, Christian A Nijhuis, Jaume Veciana
This Communication describes the mechanism of charge transport across self-assembled monolayers (SAMs) of two donor-acceptor systems consisting of a polychlorotriphenylmethyl (PTM) electron-acceptor moiety linked to an electron-donor ferrocene (Fc) unit supported by ultraflat template-stripped Au and contacted by a eutectic alloy of gallium and indium top contacts. The electronic and supramolecular structures of these SAMs were well characterized. The PTM unit can be switched between the nonradical and radical forms, which influences the rectification behavior of the junction...
March 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28252517/transanal-minimally-invasive-surgery-for-local-excision-of-benign-and-malignant-rectal-neoplasia-outcomes-from-200-consecutive-cases-with-midterm-follow-up
#9
Lawrence Lee, John P Burke, Teresa deBeche-Adams, George Nassif, Beatriz Martin-Perez, John R T Monson, Matthew R Albert, Sam B Atallah
OBJECTIVE: This study describes the outcomes for 200 consecutive transanal minimally invasive surgery (TAMIS) local excision (LE) for rectal neoplasia. BACKGROUND: TAMIS is an advanced transanal platform that can result in high quality LE of rectal neoplasia. METHODS: Consecutive patients from July 1, 2009 to December 31, 2015 from a prospective institutional registry were analyzed. Indication for TAMIS LE was endoscopically unresectable benign lesions or histologically favorable early rectal cancers...
March 1, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28191919/lysine-tryptophan-crosslinked-peptides-produced-by-radical-sam-enzymes-in-pathogenic-streptococci
#10
Kelsey R Schramma, Mohammad R Seyedsayamdost
Macrocycles represent a common structural framework in many naturally occurring peptides. Several strategies exist for macrocyclization, and the enzymes that incorporate them are of great interest, as they enhance our repertoire for creating complex molecules. We recently discovered a new peptide cyclization reaction involving a crosslink between the side chains of lysine and tryptophan that is installed by a radical SAM enzyme. Herein, we characterize relatives of this metalloenzyme from the pathogens Streptococcus agalactiae and Streptococcus suis...
March 3, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28164386/a-class-c-radical-s-adenosylmethionine-methyltransferase-synthesizes-8-methylmenaquinone
#11
Sascha Hein, Oliver Klimmek, Markus Polly, Melanie Kern, Jörg Simon
The membranous quinone/quinol pool is essential to the majority of life forms and has been widely used as an important biomarker in microbial taxonomy. In the anaerobic world, the most important quinones are menaquinone (MK) and a methylated form of MK, designated methylmenaquinone (MMK), which is anticipated to serve specifically in low-potential electron transport chains involved in anaerobic respiration. However, it has remained unclear how MMK is generated. Here, we show that a novel enzyme homologous to class C radical SAM methyltransferases (RSMTs) synthesizes MMK using MK as substrate...
February 6, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28112859/the-catalytic-mechanism-of-the-class-c-radical-s-adenosylmethionine-methyltransferase-nosn
#12
Wei Ding, Yongzhen Li, Junfeng Zhao, Xinjian Ji, Tianlu Mo, Haocheng Qianzhu, Tao Tu, Zixin Deng, Yi Yu, Fener Chen, Qi Zhang
S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an SN 2 mechanism, whereas a subset of them involves radical intermediates for methylating non-nucleophilic substrates. Herein, we report the characterization and mechanistic investigation of NosN, a class C radical SAM methyltransferase involved in the biosynthesis of the thiopeptide antibiotic nosiheptide. We show that, in contrast to all known SAM-dependent methyltransferases, NosN does not produce S-adenosylhomocysteine (SAH) as a co-product...
January 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28108243/tpx2-as-a-prognostic-indicator-and-potential-therapeutic-target-in-clear-cell-renal-cell-carcinoma
#13
Zachary A Glaser, Harold D Love, Shunhua Guo, Lan Gellert, Sam S Chang, Stanley Duke Herrell, Daniel A Barocas, David F Penson, Michael S Cookson, Peter E Clark
OBJECTIVES: Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA). METHODS: Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist...
January 17, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28093141/re-utility-and-significance-of-ureteric-frozen-section-analysis-during-radical-cystectomy
#14
Sam S Chang
No abstract text is available yet for this article.
February 2017: Journal of Urology
https://www.readbyqxmd.com/read/28067841/lectin-digestibility-and-stability-of-elderberry-antioxidants-to-heat-treatment-in-vitro
#15
Pilar Jiménez, Patricia Cabrero, Damian Cordoba-Diaz, Manuel Cordoba-Diaz, Manuel Garrosa, Tomás Girbés
Elderberry contains healthy low molecular weight nutraceuticals and lectins which are sequence-related to the elderberry allergen Sam n1. Some of these lectins are type II ribosome-inactivating proteins. The sensitivity of native lectins present in elderberry fruits and bark to the proteolysis triggered by in vitro simulated gastric and duodenal fluids has been investigated. It was found that these lectins are refractory to proteolysis. Nonetheless, incubation for 5-10 min in a boiling water bath completely sensitized them to the hydrolytic enzymes in vitro...
January 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28047832/su-d-bra-06-duodenal-interfraction-motion-with-abdominal-compression
#16
A Witztum, D Holyoake, S Warren, M Partridge, M Hawkins
PURPOSE: To quantify the effect of abdominal compression on duodenal motion during pancreatic radiotherapy. METHODS: Seven patients treated for pancreatic cancer were selected for analysis. Four patients were treated with abdominal compression and three without. The duodenum was contoured by the same physician on each CBCT (five CBCTs for patients with compression, four for non-compression patients). CBCTs were rigidly registered using a soft tissue match and contours were copied to the delivered plans which were all radical (BED > 50 Gy)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045519/7-carboxy-7-deazaguanine-synthase-a-radical-s-adenosyl-l-methionine-enzyme-with-polar-tendencies
#17
Nathan A Bruender, Tsehai A J Grell, Daniel P Dowling, Reid M McCarty, Catherine L Drennan, Vahe Bandarian
Radical S-adenosyl-l-methionine (SAM) enzymes are widely distributed and catalyze diverse reactions. SAM binds to the unique iron atom of a site-differentiated [4Fe-4S] cluster and is reductively cleaved to generate a 5'-deoxyadenosyl radical, which initiates turnover. 7-Carboxy-7-deazaguanine (CDG) synthase (QueE) catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products. 6-Carboxypterin (6-CP), an oxidized analogue of the natural substrate 6-carboxy-5,6,7,8-tetrahydropterin (CPH4), is shown to be an alternate substrate for CDG synthase...
February 8, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28045510/anaerobic-heme-degradation-chuy-is-an-anaerobilin-reductase-that-exhibits-kinetic-cooperativity
#18
Joseph W LaMattina, Michael Delrossi, Katherine G Uy, Nicholas D Keul, David B Nix, Anudeep R Neelam, William N Lanzilotta
Heme catabolism is an important biochemical process that many bacterial pathogens utilize to acquire iron. However, tetrapyrrole catabolites can be reactive and often require further processing for transport out of the cell or conversion to another useful cofactor. In previous work, we presented in vitro evidence of an anaerobic heme degradation pathway in Escherichia coli O157:H7. Consistent with reactions that have been reported for other radical S-adenosyl-l-methionine methyltransferases, ChuW transfers a methyl group to heme by a radical-mediated mechanism and catalyzes the β-scission of the porphyrin macrocycle...
January 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28040895/biosynthesis-of-branched-alkoxy-groups-iterative-methyl-group-alkylation-by-a-cobalamin-dependent-radical-sam-enzyme
#19
Yuanyou Wang, Bastien Schnell, Sascha Baumann, Rolf Müller, Tadhg P Begley
The biosynthesis of branched alkoxy groups, such as the unique t-butyl group found in a variety of natural products, is still poorly understood. Recently, cystobactamids were isolated and identified from Cystobacter sp as novel antibacterials. These metabolites contain an isopropyl group proposed to be formed using CysS, a cobalamin-dependent radical S-adenosylmethionine (SAM) methyltransferase. Here, we reconstitute the CysS-catalyzed reaction, on p-aminobenzoate thioester substrates, and demonstrate that it not only catalyzes sequential methylations of a methyl group to form ethyl and isopropyl groups but remarkably also sec-butyl and t-butyl groups...
January 25, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28027411/dna-repair-by-the-radical-sam-enzyme-spore-photoproduct-lyase-from-biochemistry-to-structural-investigations
#20
REVIEW
Olivier Berteau, Alhosna Benjdia
Radical S-adenosyl-L-methionine (SAM) enzymes have emerged as one of the last superfamilies of enzymes discovered to date. Arguably, it is the most versatile group of enzymes involved in at least 85 biochemical transformations. One of the founding members of this enzyme superfamily is the spore photoproduct (SP) lyase, a DNA repair enzyme catalyzing the direct reversal repair of a unique DNA lesion, the so-called spore photoproduct, back into two thymidine residues. Discovered more than 20 years ago in the bacterium Bacillus subtilis, SP lyase has been shown to be widespread in the endospore-forming Firmicutes from the Bacilli and Clostridia classes and to use radical-based chemistry to perform C-C bond breakage, a chemically challenging reaction...
December 27, 2016: Photochemistry and Photobiology
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