The Catalytic Mechanism and Fidelity of Herpes Primase

University Of Colorado At Boulder, Boulder CO

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Abstract

DESCRIPTION (provided by applicant): In this research, the catalytic mechanism and fidelity of herpes primase will be studied. Presently, little is known about herpes primase. A better understanding of this essential replication protein may lead to the development of new, more effective, antiviral drugs against herpes viruses. Studies of the catalytic mechanism of herpes primase will focus on 1) determining the order in which enzyme, template, and nucleotides assemble to initiate primer synthesis and 2) identifying the rate limiting step in primer synthesis. Trapping assays and a number of template/nucleotide combinations will be utilized to determine the order of binding. Steady-state and pre-steady-state kinetic experiments will be utilized to determine the rate limiting step. Experiments to determine the fidelity of herpes primase will examine the misincorporation of nucleotides in the presence and absence of cognate nucleotides.