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Title: Cutting Choline with Radical Scissors

Authors:
;
Publication Date:
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1400414
Alternate Identifier(s):
OSTI ID: 1396615
Grant/Contract Number:
FG02-10ER16194; SC0005404
Resource Type:
Journal Article: Published Article
Journal Name:
Cell Chemical Biology
Additional Journal Information:
Journal Volume: 23; Journal Issue: 10; Related Information: CHORUS Timestamp: 2017-10-19 21:06:49; Journal ID: ISSN 2451-9456
Publisher:
Elsevier
Country of Publication:
Country unknown/Code not available
Language:
English

Citation Formats

Broderick, Joan B., and Moody, James D.. Cutting Choline with Radical Scissors. Country unknown/Code not available: N. p., 2016. Web. doi:10.1016/j.chembiol.2016.10.002.
Broderick, Joan B., & Moody, James D.. Cutting Choline with Radical Scissors. Country unknown/Code not available. doi:10.1016/j.chembiol.2016.10.002.
Broderick, Joan B., and Moody, James D.. Sat . "Cutting Choline with Radical Scissors". Country unknown/Code not available. doi:10.1016/j.chembiol.2016.10.002.
@article{osti_1400414,
title = {Cutting Choline with Radical Scissors},
author = {Broderick, Joan B. and Moody, James D.},
abstractNote = {},
doi = {10.1016/j.chembiol.2016.10.002},
journal = {Cell Chemical Biology},
number = 10,
volume = 23,
place = {Country unknown/Code not available},
year = {Sat Oct 01 00:00:00 EDT 2016},
month = {Sat Oct 01 00:00:00 EDT 2016}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.chembiol.2016.10.002

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  • Restriction enzymes have been the workhorses of genetic engineering for nearly 20 years now. These enzymes which cut DNA at very specific sites, have made possible the astounding progress in gene cloning and sequencing. But indispensable as they are, these scissors have their limitations. Even the best among them, the rare cutters, chop big chunks of DNA into too many pieces for easy handling. The problem is becoming particular acute now that researchers are gearing up to map and sequence the very large genomes of humans and other complex organisms. Researchers at the University of Wisconsin have come up withmore » a simple solution to this long-standing problem in genetic engineering. They have created a new type of scissors that will cut a huge piece of DNA exactly where they want and no place else. Their technique promises to become a new tool for dissecting large genomes.« less
  • We report that deamination of choline catalyzed by the glycyl radical enzyme choline trimethylamine-lyase (CutC) has emerged as an important route for the production of trimethylamine, a microbial metabolite associated with both human disease and biological methane production. Here, we have determined five high-resolution X-ray structures of wild-type CutC and mechanistically informative mutants in the presence of choline. Within an unexpectedly polar active site, CutC orients choline through hydrogen bonding with a putative general base, and through close interactions between phenolic and carboxylate oxygen atoms of the protein scaffold and the polarized methyl groups of the trimethylammonium moiety. These structuralmore » data, along with biochemical analysis of active site mutants, support a mechanism that involves direct elimination of trimethylamine. Lastly, this work broadens our understanding of radical-based enzyme catalysis and will aid in the rational design of inhibitors of bacterial trimethylamine production.« less
  • Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic {sup 18}F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up tomore » total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, {sup 18}F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.« less