Twisting of the DNA-binding surface by a β-strand-bearing proline modulates DNA gyrase activity
Journal
Nucleic Acids Research
Journal Volume
38
Journal Volume
38
Journal Issue
12
Journal Issue
12
Pages
4173-4181
Start Page
4173
End Page
4181
ISSN
13624962
Date Issued
2010-03-09
Author(s)
Hsieh, Tung-Ju
Yen, Tien-Jui
Lin, Te-Sheng
Chang, Hsun-Tang
Huang, Shu-Yun
Farh, Lynn
Chan, Nei-Li
Abstract
DNA gyrase is the only topoisomerase capable of introducing (-) supercoils into relaxed DNA. The C-terminal domain of the gyrase A subunit (GyrA-CTD) and the presence of a gyrase-specific 'GyrA-box' motif within this domain are essential for this unique (-) supercoiling activity by allowing gyrase to wrap DNA around itself. Here we report the crystal structure of Xanthomonas campestris GyrA-CTD and provide the first view of a canonical GyrA-box motif. This structure resembles the GyrA-box-disordered Escherichia coli GyrA-CTD, both adopting a non-planar beta-pinwheel fold composed of six seemingly spirally arranged beta-sheet blades. Interestingly, structural analysis revealed that the non-planar architecture mainly stems from the tilted packing seen between blades 1 and 2, with the packing geometry likely being defined by a conserved and unusual beta-strand-bearing proline. Consequently, the GyrA-box-containing blade 1 is placed at an angled spatial position relative to the other DNA-binding blades, and an abrupt bend is introduced into the otherwise flat DNA-binding surface. Mutagenesis studies support that the proline-induced structural twist contributes directly to gyrase's (-) supercoiling activity. To our knowledge, this is the first demonstration that a beta-strand-bearing proline may impact protein function. Potential relevance of beta-strand-bearing proline to disease phenylketonuria is also noted.
SDGs
Type
journal article