Methods and compositions for determining enzymatic activity and specificity of methlytransferases
AssigneesThe Salk Institute for Biological Studies, The Samuel Roberts Noble Foundation
InventorsJoseph P Noel, Chloe Zubieta, Richard Dixon
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Abstract
The invention provides crystalline O-methyltransferases and isolated non-native O-methyltransferases as well as sets of their structural coordinates. Also provided are methods of predicting the activity or substrate specificity of putative O-methyltransferases, methods of identifying potential substrates of O-methyltransferases, and methods of identifying potential inhibitors of methyltranferases.
Claims23
A method of predicting the activity and/or substrate specificity of a putative O-methyltransferase, said method comprising:
- comparing a three-dimensional representation of a known O-methyltransferase and the three-dimensional representation of said putative O-methyltransferase, wherein similarities and/or differences between the two representations are predictive of O-methyltransferase activity and/or substrate specificity.
A crystalline form of an O-methyltransferase having a set of structural coordinates as set forth in Appendix A, Appendix B, Appendix C, Appendix D, PDB Accession No:
- 1FPQ, PDB Accession No:1FPX, PDB Accession No:1FP1, or PDB Accession No:1FP2.
A crystalline complex comprising an O-methyltransferase and an O-methyltransferase substrate.
A method of identifying a potential substrate of an O-methyltransferase, said method comprising:
- (a) defining an active site of said O-methyltransferase based on a plurality of atomic coordinates of said O-methyltransferase;
- (b) identifying a potential substrate that fits the active site of (a);
- and
- (c) contacting the O-methyltransferase with the potential substrate and determining its activity thereon.
A method of identifying a potential inhibitor of an O-methyltransferase, said method comprising:
- (a) contacting a potential compound that fits an active site based on a plurality of atomic coordinates of said O-methyltransferase;
- and
- (b) determining the ability of said compound to inhibit the activity of said O-methyltransferase.
A computer program on a computer readable medium, said computer program comprising instructions to cause a computer to:
- define an O-methyltransferase or fragment thereof based on a plurality of atomic coordinates of the O-methyltransferase.
Dependencies are inferred from the claim text.