Crystal structure of a deacetylase and inhibitors thereof

C - Chemistry – Metallurgy – 12 – N

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C12N 15/12 (2006.01) C07K 14/00 (2006.01) C12N 9/16 (2006.01) G01N 33/573 (2006.01)

Patent

CA 2383885

The present invention provides three-dimensional structural information from the hyperthermophilic bacterium Aquifex aeolicus which is a histone deacetylase-like protein (HDLP). HDLP shares 35.2% amino acid sequence identity with human histone deacetylase (HDAC1). The present invention further provides three-dimensional structural information of HDLP bound by inhibitor molecules. The three-dimensional structural information of the present invention is useful to design, isolate and screen deacetylase inhibitor compounds capable of inhibiting HDLP, HDAC family members and HDLP-related molecules. The invention also relates to nucleic acids encoding a mutant HDLP which facilitates the determination of the three-dimensional structure of HDLP in the presence of a zinc atom.

La présente invention concerne des informations structurelles tridimensionnelles tirées de la bactérie hyperthermophile Aquifex aeolcius qui est une protéine histone de type déacétylase (HDLP). La HDLP partage 35,2 % d'identité de séquence amino-acide avec l'histone déacetylase humaine (HDAC1). Cette invention fournit également des informations structurelles tridimensionnelles de la HDLP liées par des molécules inhibitrices. Les informations structurelles tridimensionnelles de la présente invention sont utiles pour la conception, l'isolement et le criblage des composés inhibiteurs déacetylase pouvant inhiber la HDLP, les membres de la famille HDAC et les molécules relatives à la HDLP. L'invention concerne également des acides nucléiques codant la HDLP mutante qui facilite la détermination de la structure tridimensionnelle de la HDLP en présence d'un atome de zinc.

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