title: An open conformation of the Thermus thermophilus gyrase B ATP-binding domain.
abstract: DNA gyrase forms an A(2)B(2) tetramer involved in DNA replication, repair, recombination, and transcription in which the B subunit catalyzes ATP hydrolysis. The Thermus thermophilus and Escherichia coli gyrases are homologues and present the same catalytic activity. When compared with that of the E. coli 43K-5'-adenylyl-beta,gamma-imidodiphosphate complex, the crystal structure of Gyrase B 43K ATPase domain in complex with novobiocin, one of the most potent inhibitors of gyrase shows large conformational changes of the subdomains within the dimer. The stabilization of loop 98-118 closing the active site through dimeric contacts and interaction with domain 2 allows to observe novobiocin-protein interactions that could not be seen in the 24K-inhibitor complexes. Furthermore, this loop adopts a position which defines an "open" conformation of the active site in absence of ATP, in contrast with the "closed" conformation adopted upon ATP binding. All together, these results indicate how the subdomains may propagate conformational changes from the active site and provide crucial information for the design of more specific inhibitors.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire, CNRS/INSERM/ULP, BP163, 1 rue Laurent Fries, 67404 Illkirch Cedex, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lamour
authors.forename: Laurence
authors.initials: L
authors.lastname: Hoermann
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Jeltsch
authors.forename: Pierre
authors.initials: P
authors.lastname: Oudet
authors.forename: Dino
authors.initials: D
authors.lastname: Moras
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D002384:Catalysis; D003374:Coumarins / Q000494:pharmacology; D027081:DNA Gyrase / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006868:Hydrolysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D016963:Thermus thermophilus / Q000201:enzymology*; D059005:Topoisomerase II Inhibitors
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D000255:Adenosine Triphosphate; C030123:coumarin; D027081:DNA Gyrase