There are three structures known for human topoisomerase - a noncovalently bound topoisomerase I, a covalently bound topoisomerase I, and a second noncovalent complex with a 70kDa form of topoisomerase.  The structures were determined using six different crystal forms and over 1000 crystals were examined using an X-ray beam (Redinbo, 1998).

This is the covalently bound topoisomerase I.  Its structure was determined at 2.1 Å reasp;itopm/It is composed of four domains which temporarily clamp around the DNA.  In its closed form it contains a central DNA-binding pore of 15 to 20 Å in diameter.   Subdomains I, II, and III constitute the 56-kD core which is closely associated with the carboxy-terminal domain.  Subdomain I consists two alpha helices and nine ß strands.   Subdomain II is composed of five alpha helices and two ß strands.  Subdomains I and II fold tightly together and form the top half or cap of the enzyme (Redinbo, 1998).  These domains also contain the two long "nose-cone" helices that come together in a "V".  Subdomain III is a complex arrangement of 10 alpha helices and 3 ß strands.  This subdomain contains all of the active-site residues except the catalytic tyrosine.   The two long alpha helices most likely function as a hinge that opens and closes the enzyme around the DNA.  The core of the enzyme interacts closely with the carboxy-terminal domain.  The compact COOH-terminal domain is composed of five short alpha helices, and contains the active-site tyrosine 723.  The central pore of the molecule is composed largely of positively charged residues, 15 lysines and 8 arginines, which give rise to a high positive electrostatic potential surrounding the pore (Redinbo, 1998)

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Updated:  December 5, 1998

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