TY - JOUR
T1 - The C-terminal domain of DNA gyrase A adopts a DNA-bending β-pinwheel fold
AU - Corbett, Kevin D.
AU - Shultzaberger, Ryan K.
AU - Berger, James M.
PY - 2004/5/11
Y1 - 2004/5/11
N2 - DNA gyrase is unique among enzymes for its ability to actively introduce negative supercoils into DNA. This function is mediated in part by the C-terminal domain of its A subunit (GyrA CTD). Here, we report the crystal structure of this ≈35-kDa domain determined to 1.75-Å resolution. The GyrA CTD unexpectedly adopts an unusual fold, which we term β-pinwheel, that is globally reminiscent of a β-propeller but is built of blades with a previously unobserved topology. A large, conserved basic patch on the outer edge of this domain suggests a likely site for binding and bending DNA; fluorescence resonance energy transfer-based assays show that the GyrA CTD is capable of bending DNA by ≥180° over a 40-bp region. Surprisingly, we find that the CTD of the topoisomerase IV A subunit, which shares limited sequence homology with the GyrA CTD, also bends DNA. Together, these data provide a physical explanation for the ability of DNA gyrase to constrain a positive superhelical DNA wrap, and also suggest that the particular substrate preferences of topoisomerase IV might be dictated in part by the function of this domain.
AB - DNA gyrase is unique among enzymes for its ability to actively introduce negative supercoils into DNA. This function is mediated in part by the C-terminal domain of its A subunit (GyrA CTD). Here, we report the crystal structure of this ≈35-kDa domain determined to 1.75-Å resolution. The GyrA CTD unexpectedly adopts an unusual fold, which we term β-pinwheel, that is globally reminiscent of a β-propeller but is built of blades with a previously unobserved topology. A large, conserved basic patch on the outer edge of this domain suggests a likely site for binding and bending DNA; fluorescence resonance energy transfer-based assays show that the GyrA CTD is capable of bending DNA by ≥180° over a 40-bp region. Surprisingly, we find that the CTD of the topoisomerase IV A subunit, which shares limited sequence homology with the GyrA CTD, also bends DNA. Together, these data provide a physical explanation for the ability of DNA gyrase to constrain a positive superhelical DNA wrap, and also suggest that the particular substrate preferences of topoisomerase IV might be dictated in part by the function of this domain.
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U2 - 10.1073/pnas.0401595101
DO - 10.1073/pnas.0401595101
M3 - Article
C2 - 15123801
AN - SCOPUS:2442611949
SN - 0027-8424
VL - 101
SP - 7293
EP - 7298
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -