2HKJ

Topoisomerase VI-B bound to radicicol

Summary for 2HKJ

• Entry DOI: 10.2210/pdb2hkj/pdb
• Related: 1MU5 1MX0
• Descriptor: Type II DNA topoisomerase VI subunit B, MAGNESIUM ION, DIMETHYL SULFOXIDE, ... (5 entities in total)
• Functional Keywords: topoisomerase, ghkl, drug complex, radicicol, isomerase
• Biological source: Sulfolobus shibatae
• Total number of polymer chains: 1
• Total formula weight: 53977.58

Authors

Corbett, K.D.,Berger, J.M. (deposition date: 2006-07-04, release date: 2006-08-29, Last modification date: 2023-08-30)

Primary citation

Corbett, K.D.,Berger, J.M.
Structural basis for topoisomerase VI inhibition by the anti-Hsp90 drug radicicol
Nucleic Acids Res., 34:4269-4277, 2006

PubMed Abstract: Members of the GHL ATPase superfamily, including type II topoisomerases, Hsp90-class chaperones, and MutL, all share a common GHKL-type ATP-binding fold and act as nucleotide-controlled 'molecular clamps'. These enzymes' ATP-binding sites have proven to be rich drug targets, and certain inhibitors of type II topoisomerases and Hsp90 bind to this region and competitively inhibit these enzymes. Recently, it was found that radicicol, a drug known to block Hsp90 function, also inhibits the archaeal type IIB topoisomerase topo VI. Here, we use X-ray crystallography to show that despite low sequence identity ( approximately 10-12%) between topo VI and Hsp90, radicicol binds to the ATPase sites of these two enzymes in an equivalent manner. We further demonstrate that radicicol inhibits both the dimerization of the topo VI ATPase domains and ATP hydrolysis, two critical steps in the enzyme's strand passage reaction. This work contributes to a growing set of structures detailing the interactions between GHL-family proteins and various drugs, and reveals radicicol as a versatile scaffold for targeting distantly related GHL enzymes.

PubMed: 16920739
DOI: 10.1093/nar/gkl567

Experimental method

X-RAY DIFFRACTION (2 Å)