2hkj
From Proteopedia
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Topoisomerase VI-B bound to radicicol
Overview
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.
About this Structure
2HKJ is a Single protein structure of sequence from Sulfolobus shibatae with , and as ligands. Active as DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3 Full crystallographic information is available from OCA.
Reference
Structural basis for topoisomerase VI inhibition by the anti-Hsp90 drug radicicol., Corbett KD, Berger JM, Nucleic Acids Res. 2006;34(15):4269-77. Epub 2006 Aug 18. PMID:16920739
Page seeded by OCA on Thu Feb 21 17:42:50 2008
