InterPro: IPR006691 DNA gyrase/topoisomerase IV, subunit A, C-terminal beta-pinwheel

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [1, 2]. DNA topoisomerases are divided into two classes: type I enzymes (EC:5.99.1.2; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (EC:5.99.1.3; topoisomerases II, IV and VI) break double-strand DNA [3].

Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils [4].

This entry represents the beta-pinwheel repeat found at the C-terminal end of subunit A of topoisomerase IV (ParC) and subunit A of DNA gyrase (GyrA). DNA gyrase is the topoisomerase II found primarily in bacteria and archaea that consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. This is distinct from the topoisomerase II found in most eukaryotes, which consists of a single polypeptide, with the N- and C-terminal regions corresponding to gyrB and gyrA, respectively, and which is not represented in this entry.

The ability of DNA gyrase to introduce negative supercoils into DNA is mediated in part by the C-terminal domain of subunit A, which forms a beta-pinwheel fold that is similar to a beta-propeller but with a different blade topology, and which forms a superhelical spiral domain [5, 6]. This beta-pinwheel is capable of bending DNA by over 180 degrees over a 40 bp region, possibly by wrapping the DNA around the GyrA C-terminal beta-pinwheel domain.

In topoisomerase IV, although the C-terminal domain forms a similar superhelical spiral to that of DNA gyrase A, it assembles as a broken form of a beta-pinwheel as distinct from that of gyrA, due to the absence of a DNA gyrase-specific GyrA box motif [7]. This difference may account for parC being less efficient than gyrA in mediating DNA-bending, leading to their divergence in terms of activity, where topoisomerase IV acts to relax positive supercoils, and DNA gyrase acts to introduce negative supercoils [8].

More information about this protein can be found at Protein of the Month: DNA Topoisomerase [9].