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elation exists only for a subset of proteins Some folds (ferredoxin, TIM barrel, …) are very popular – several protein families, with diverse functions, adopt these folds Well, no!! Detailed biochemical characterization is required Despite high similarity in sequence and structure, may act on different substrates (hence different functions) – due to subtle changes in active site (b1?3GalT and b1?3GlcNAcT) Similar structure, mutually exclusive function: Lysozyme amp。 alactalbumin Inferring Function from Structure: Caveats Same function, pletely different structures: Carbonic anhydrases from M. thermophila and mouse , “Moonlighting” proteins – one structure(?), multiple functions Glyceraldehyde 3phosphate dehydrogenase Glycolysis Binding protein for plasmin, fibronectin and lysozyme Transcriptional control of gene expression, DNA replication and repair Flocculation Gal1p – Kinase as well as regulator of Galgene expression Gal3p – 70% similar。 does not have kinase activity Same fold, different oligomerization Dimerization Tetramerization ConA ConA PNA PNA, GSIV Ligand Induced Conformational Changes are Quite Common Binding of first substrate redefines the active site and creates the binding pocket for the second substrate and the metal ion Flexible loop Before After Take Home Message Predicting Protein Structure is a key ponent of genome sequence analysis Structure is a very important link in deciphering the function New tools are required? Or larger training dataset is required? Acknowledgement Organizers for giving me this opportunity Sujatha and Jayadeva Bhat for helping me put together this talk Few Useful Links