Twisting of the DNA-binding surface by a beta-strand-bearing proline modulates DNA gyrase activity.
Nucleic Acids Res
; 38(12): 4173-81, 2010 Jul.
Article
in En
| MEDLINE
| ID: mdl-20215433
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.
Full text:
1
Database:
MEDLINE
Main subject:
Proline
/
Xanthomonas campestris
/
DNA Gyrase
/
DNA-Binding Proteins
Language:
En
Journal:
Nucleic Acids Res
Year:
2010
Type:
Article
Affiliation country:
Taiwan