HSP90 - C Terminal Domain

Biochemical studies have shown that the C-terminal domain of Hsp90 contains another ATP-binding site that is only available when the N-terminal domain ATP binding site is occupied. No C-terminal domain bound to inhibitor co-crystal has been reported. The C-terminal also has a conserved MEEVD sequence that is known to recognise co-chaperones. Co-chaperones assist and act as regulators of Hsp90's activity. This co-chaperone binding site is being studied in hope of creating novel therapeutic drugs: "EGCG is one of the active ingredients found in green tea. EGCG is known to inhibit the activity of many Hsp90-dependent client proteins, including telomerase, several kinases, and the aryl hydrocarbon receptor (AhR). Recently Gasiewicz and co-workers reported that EGCG manifests its antagonistic activity against AhR through binding Hsp90."

For information on the biochemical studies of the C-terminal ATP binding domain, see "A Nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. N-terminal nucleotide binding unmasks a C-terminal binding pocket".

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