Crystal structure of the (AML1 Runt domain)/(CBFBETA) heterodimer and the ternary complex with DNA

A crystal comprising CBFβ.

A crystal comprising the regions of AML1 Runt domain which are involved in heterodimerisation with CBFβ.

A crystal comprising the regions of CBFβ which are involved in heterodimerisation with AML1.

A crystal having the structure co-ordinates as shown in Table 3 or Table 4.

A method of screening for a ligand capable of binding the AML1 Runt domain and/or CBFβ, comprising analyzing the three dimensional structure of said AML1 Runt domain and/or CBFβ subunit by a computer modeling program.

A method of screening for a ligand capable of modulating the DNA-binding capacity of the AML1 Runt domain, comprising analyzing the three dimensional structure of said AML1 Runt domain by a computer modeling program.

A method for producing a medicament to treat and/or prevent a disease in a mammal comprising:

• (a) analyzing the three dimensional structure of an AML1 Runt domain and/or CBFβ subunit by a computer modeling program so as to identify a ligand which is capable of interacting with said AML1 Runt domain and/or CBFβ subunit;
• (b) mixing said ligand with a pharmaceutically acceptable carrier.

A method for the treatment and/or prevention of a disease associated with chromosomal translocations involving the AML1 and/or the CBFB gene, comprising administering to an animal in need of said treatment and/or prevention a pharmaceutical formulation comprising a ligand which is capable of interacting with an AML1 Runt domain and/or CBFβ subunit, and a pharmaceutical carrier.