CPC C12N 9/14 (2013.01) [C12N 9/90 (2013.01); C12Y 306/04012 (2013.01); C12P 19/34 (2013.01)] | 8 Claims |
1. A method of catalyzing an unwinding reaction of a double-stranded DNA, comprising contacting the double-stranded DNA with a conformationally-constrained helicase
wherein the conformationally-constrained helicase is selected from the group consisting of a Rep helicase from E. coli, a UvrD helicase from E. coli, a PcrA helicase from B. stearothermophilus, or a homolog thereof;
wherein the conformationally-constrained helicase comprises a first subdomain comprising a 1A or a 1B subdomain having a first amino acid and a second subdomain comprising a 2B subdomain having a second amino acid,
wherein the first amino acid corresponds to any one of positions 84-116 or 178-196 of the helicase amino acid sequence, relative to SEQ ID NO:32;
wherein the second amino acid corresponds to any one of positions 388-411, 422-444, and 518-540 of the helicase amino acid sequence, relative to SEQ ID NO:32;
wherein a side chain of the first amino acid is covalently crosslinked to a side chain of the second amino acid with a linker to form an active, conformationally-constrained helicase;
wherein said first amino acid is less than about 20 Å from said second amino acid when the helicase is in an active conformation, and
wherein the conformationally-constrained helicase comprises at least one degree of freedom less than a helicase that is not constrained as such.
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