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New Molecular Mechanics Study Results from Michigan State University Described (Mechanistic Insights into Mg2+-Independent Prenylation by CloQ from...

September 2, 2014



New Molecular Mechanics Study Results from Michigan State University Described (Mechanistic Insights into Mg2+-Independent Prenylation by CloQ from Classical Molecular Mechanics and Hybrid Quantum Mechanics/Molecular Mechanics Molecular ...)

By a News Reporter-Staff News Editor at Physics Week -- Investigators publish new report on Molecular Mechanics. According to news reporting out of East Lansing, Michigan, by VerticalNews editors, research stated, "Understanding the mechanism of prenyltransferases is important to the design of engineered proteins capable of synthesizing derivatives of naturally occurring therapeutic agents. CloQ is a Me-independent aromatic prenyltransferase (APTase) that transfers a dimethylallyl group to 4-hydroxyphenylpyruvate in the biosynthetic pathway for clorobiocin."

Our news journalists obtained a quote from the research from Michigan State University, "APTases consist of a common ABBA fold that defines a beta-barrel containing the reaction cavity. Positively charged basic residues line the inside of the beta-barrel of CloQ to activate the pyrophosphate leaving group to replace the function of the Mg2+ cofactor in other APTases. Classical molecular dynamics simulations of CloQ, its E281G and F68S mutants, and the related NovQ were used to explore the binding of the 4-hydroxyphenylpyruvate (4HPP) and dimethylallyl diphosphate substrates in the reactive cavity and the role of various conserved residues. Hybrid quantum mechanics/molecular mechanics potential of mean force (PMF) calculations show that the effect of the replacement of the Mg2+ cofactor with basic residues yields a similar activation barrier for prenylation to Me-dependent APTases like NphB. The topology of the binding pocket for 4HPP is important for selective prenylation at the ortho position of the ring. Methylation at this position alters the conformation of the substrate for O-prenylation at the phenol group."

According to the news editors, the research concluded: "Further, a two-dimensional PMF scan shows that a 'reverse' prenylation product may be a possible target for protein engineering."

For more information on this research see: Mechanistic Insights into Mg2+-Independent Prenylation by CloQ from Classical Molecular Mechanics and Hybrid Quantum Mechanics/Molecular Mechanics Molecular Dynamics Simulations. Biochemistry, 2014;53(30):5034-5041. Biochemistry can be contacted at: Amer Chemical Soc, 1155 16TH St, NW, Washington, DC 20036, USA. (American Chemical Society - www.acs.org; Biochemistry - www.pubs.acs.org/journal/bichaw)

Our news journalists report that additional information may be obtained by contacting C.A. Bayse, Michigan State University, Dept. of Biochem & Mol Biol, East Lansing, MI 48824, United States.

Keywords for this news article include: Michigan, East Lansing, United States, Nanotechnology, Quantum Physics, Quantum Mechanics, Molecular Dynamics, Molecular Mechanics, Emerging Technologies, North and Central America

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Physics Week


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