Crystal structure of interleukin-22 and uses thereof
OwnerRonaldo A.P. Nagem, Igor Polikarpov +3inventors
InventorsRonaldo A.P. Nagem, Igor Polikarpov, Jean Christophe Renauld, Didier Colau, Laure Dumoutier
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Abstract
This invention provides the three dimensional structure of human IL-22 and recombinant human IL-22 with mutations in the receptor binding regions and the dimerization interface and nucleic acid molecule encoding same. This invention also relates to methods of using pharmaceutical formulations and mimetics of the recombinant IL-22 and to methods for generating mutants based on the crystalline structure of IL-22.
Claims28
A method for identifying a mutant mammalian IL-22 with modified ability to dimerize and/or bind an IL-22 receptor, said method comprising the steps of:
- a) constructing a three-dimensional structure of hIL-22 defined by the atomic coordinates shown in Table 4;
- b) employing the three-dimensional structure and modeling methods to identify an amino acid involved in stabilizing an IL-22 dimer, and/or to identify an amino acid involved in receptor binding;
- c) producing a mammalian IL-22 having a mutation at an amino acid identified in (b);
- and
- d) assaying said mutant IL-22 to determine the ability of said mutant to dimerize as compared to an IL-22 control, wherein a difference in dimerization between said mutant and said control is indicative of a modified ability to dimerize, and/or assaying said mutant IL-22 to determine the ability of said mutant to bind to the IL-22 receptor as compared to an IL-22 control, wherein a difference in binding between said mutant and said IL-22 control is indicative of a modified ability to bind the IL-22 receptor.
A mutant IL-22 comprising at least one amino acid substitution in Region 1 or Region 2.
A mutant IL-22 comprising at least one mutation at an IL-22 dimerization interface.
A method for determining ability of a substance of interest to bind to interleukin-22 (IL-22) or a mutant form of IL-22, comprising:
- (i) employing computational means to perform a fitting operation between said substance of interest and a predetermined binding pocket of said IL-22 or mutant form thereof;
- and
- (ii) analyzing results obtained in (i) to quantify association therebetween as a determination of ability of said substance to bind to IL-22 or the mutant form thereof.
A machine readable, storage medium comprising a data storage medium that contains machine readable data, said machine readable data comprising at least a portion of structural coordinates of IL-22 or a mutant form thereof.
Dependencies are inferred from the claim text.