Protein crystal structure
OwnerSteven Gamblin, Jonathan Wilson +4inventors
InventorsSteven Gamblin, Jonathan Wilson, Philip Walker, Chun Jing, George Blackburn, Bing Xiao
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Abstract
Disclosed is a crystal comprising at least a catalytically active portion of a SET 7/9 histone methyltransferase, and various uses thereof, and ligands for SET 7/9.
Claims37
A crystal comprising at least a catalytically active portion of a SET 7/9 histone methyltransferase.
A method of selecting or designing a ligand for SET 7/9, which method comprises use of at least part of the atomic co-ordinate data contained in Annex 1 or data derivable therefrom.
A computer system and/or a computer readable medium comprising positional data relating to, or derivable form, at least part of the atomic co-ordinate data contained in Annex 1.
A method of forming a crystal comprising at least part of a SET 7/9 domain, the method comprising the steps of:
- forming a complex comprising at least a catalytically active portion of a SET 7/9 domain and a lysine-containing substrate peptide or protein;
- and crystallising the complex.
A ligand for SET 7/9 conforming to general formula I or II:
- wherein R1, R2 and R3 are, independently:
- H, alkyl, haloakyl, aralkyl, acyl, cycloalkyl, alkenyl, or oxa-alkyl and wherein n=0, 1 or 2.
- wherein R1-R3 and are as in general formula I, and wherein R4 may be selected from any of the following:
- a linear, cyclic or branched alkyl group comprising 2 or more carbon atoms (preferably 2-6 carbon atoms, more preferably 2-5 carbon atoms);
- an alkenyl group having one or more double bonds;
- the alkyl or alkenyl group optionally being substituted at one or more positions (e.g. hydroxylated, halogenated, or aminated) and optionally comprising one or more oxa- aza- or thia-replacements of CH2 groups.
A ligand for SET 7/9 comprising a bis-bicyclooctane or a 1,4 diphenyl moiety.
A ligand for SET 7/9 in accordance with the structure shown in FIG. 5 or FIG. 6.
A method of altering the substrate specificity of histone methyltransferases, the method comprising the steps of:
- obtaining a nucleotide sequence encoding at least a catalytically active portion of a SET HMT;
- and altering the nucleotide sequence so as to introduce a mutation at one or more residues selected from the group consisting of residue numbers;
- 245;
- 305;
- and 335.
Dependencies are inferred from the claim text.