Comparison of the topoisomerase active site of type IB and IC enzymes.
A, stereo view of the active site of human topoisomerase I (Protein Data Bank entry 1A35) (41), a type IB enzyme (green) bound to DNA (blue). The catalytic pentad consists of Tyr-723 (mutated to Phe-723 in the present structure), His-632, Lys-532, Arg-488, and Arg-590. The corresponding residues of vaccinia topoisomerase are Tyr-274, His-265, Lys-167, Arg-131, and Arg-223. B, stereo view of the topoisomerase active site of an N-terminal 61-kDa fragment (Topo-61; Protein Data Bank entry 2CSB) (8) of Topo-V, a type IC enzyme. The core topoisomerase domain is in red, and the (HhH)2 domains are shown in yellow and magenta. The active site pentad consists of Tyr-226, His-200, Lys-218, Arg-131, and Arg-144. Glu-215 is also seen in the active site vicinity. A superposition of type IB and IC enzymes shows that the tyrosine and the two arginines are at similar positions in the active sites but the lysine and the histidine are not superimposable.