Crystal Structure of Human Proliferating Cell Nuclear Antigen (Pcna) and Uses Thereof
OwnerGeorge Kontopidis, Daniella I. Zheleva +3inventors
InventorsGeorge Kontopidis, Daniella I. Zheleva, Campbell McInnes, Peter Martin Fischer, Malcolm Douglas Walkinshaw
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Abstract
The present invention relates to crystals comprising human PCNA, and methods and assays for designing and identifying small molecule PCNA inhibitors using said crystals.
Claims66
A crystal comprising human proliferating cell nuclear antigen (PCNA).
A crystal comprising a human PCNA ligand binding domain.
An assay for a candidate compound capable of modulating PCNA, said assay comprising the steps of:
- (a) contacting said candidate compound with PCNA;
- (b) detecting whether said candidate compound forms associations with one or more amino acid residues corresponding to PCNA amino acid residues I255, P253, A252, Y250, P234, P129, G127, L126, Q125, L47, V45, H44, W227 and W364.
(canceled)
A computer for producing a three-dimensional representation of PCNA wherein said computer comprises:
- (a) a computer-readable data storage medium comprising a data storage material encoded with computer-readable data, wherein said data comprises the structure co-ordinates of Table 3, Table 4 and/or Table 5;
- (b) a working memory for storing instructions for processing said computer-readable data;
- (c) a central-processing unit coupled to said working memory and to said computer-readable data storage medium for processing said computer-machine readable data into said three-dimensional representation;
- and
- (d) a display coupled to said central-processing unit for displaying said three-dimensional representation.
A machine-readable data storage medium comprising a data storage material encoded with machine readable data, wherein the data is defined by at least a portion of the structure co-ordinates of Table 3, Table 4 and/or Table 5.
A method for screening for modulators of PCNA, comprising using at least a portion of the structure co-ordinates of Table 3, Table 4 and/or Table 5, such modulators of PCNA are screened.
56 A method for designing, selecting and synthesizing modulators of PCNA, comprising using at least a portion of the structure co-ordinates of Table 3, Table 4 and/or Table 5 in molecular design techniques, such that modulators of PCNA are designed, selected and synthesized.
A method of identifying chemical entities or compounds that modulate PCNA, comprising using at least a portion of the structure co-ordinates of Table 3, Table 4 and/or Table 5 to screen small molecule databases for chemical entities or compounds that modulate PCNA, such that chemical entities or compounds that modulate PCNA are identified.
A method of solving the structure of a crystalline form of a protein, comprising using at least a portion of the structure co-ordinates of Table 3, Table 4 and/or Table 5 to solve the structure of the crystalline form of a protein, wherein said protein has significant amino acid sequence homology to any functional domain of PCNA.
A fragment of PCNA, or a homologue, mutant, or derivative thereof, comprising a ligand binding domain, said ligand binding domain being defined by the amino acid residue structural coordinates selected from one or more of the following:
- I255, P253, A252, Y250, P234, P129, G127, L126, Q125, L47, V45, H44, W227 and W364.
66-69. (canceled)
Dependencies are inferred from the claim text.