The NTIS website and supporting ordering systems are undergoing a major upgrade from 8PM on September 25th through approximately October 6. During that time, much of the functionality, including subscription and product ordering, shipping, etc., will not be available. You may call NTIS at 1-800-553-6847 or (703) 605-6000 to place an order but you should expect delayed shipment. Please do NOT include credit card numbers in any email you might send NTIS.
Documents in the NTIS Technical Reports collection are the results of federally funded research. They are directly submitted to or collected by NTIS from Federal agencies for permanent accessibility to industry, academia and the public.  Before purchasing from NTIS, you may want to check for free access from (1) the issuing organization's website; (2) the U.S. Government Printing Office's Federal Digital System website http://www.gpo.gov/fdsys; (3) the federal government Internet portal USA.gov; or (4) a web search conducted using a commercial search engine such as http://www.google.com.
Accession Number ADA565098
Title Tyrosine Phosphorylation of Botulinum Neurotoxin Protease Domains.
Publication Date Jun 2012
Media Count 13p
Personal Author E. E. Brueggmann G. A. Oyler H. B. Hines L. A. Smith S. Toth
Abstract Botulinum neurotoxins are most potent of all toxins. Their N- terminal light chain domain (Lc) translocates into peripheral cholinergic neurons to exert its endoproteolytic action leading to muscle paralysis. Therapeutic development against these toxins is a major challenge due to their in vitro and in vivo structural differences. Although three-dimensional structures and reaction mechanisms are very similar, the seven serotypes designated A through G vastly vary in their intracellular catalytic stability. To investigate if protein phosphorylation could account for this difference, we employed Src-catalyzed tyrosine phosphorylation of the Lc of six serotypes namely LcA, LcB, LcC1, LcD, LcE, and LcG. Very little phosphorylation was observed with LcD and LcE but LcA, LcB, and LcG were maximally phosphorylated by Src. Phosphorylation of LcA, LcB, and LcG did not affect their secondary and tertiary structures and thermostability significantly. Phosphorylation of Y250 and Y251 made LcA resistant to autocatalysis and drastically reduced its kcat/Km for catalysis. A tyrosine residue present near the essential cysteine at the C-terminal tail of LcA, LcB, and LcG was readily phosphorylated in vitro. Inclusion of a competitive inhibitor protected Y426 of LcA from phosphorylation, shedding light on the role of the C-terminus in the enzyme s substrate or product binding.
Keywords Botulinum neurotoxin
Catalysis
Clostridium botulinum
Nerve cells
Neurotoxins
Phosphorylation
Protease
Protein phosphorylation
Proteins
Reprints
Tyrosine
Tyrosine phosphorylation
Zinc endoporotease


 
Source Agency Non Paid ADAS
NTIS Subject Category 57K - Microbiology
57B - Biochemistry
Corporate Author Army Medical Research Inst. of Infectious Diseases, Fort Detrick, MD.
Document Type Journal article
Title Note Journal article.
NTIS Issue Number 1304
Contract Number N/A

Science and Technology Highlights

See a sampling of the latest scientific, technical and engineering information from NTIS in the NTIS Technical Reports Newsletter

Acrobat Reader Mobile    Acrobat Reader