Linking Sequence and Structure
with Function

UCSF
The California Institute for Quantitative Biomedical Research (QB3)
1700 4th Street, 5th Floor
San Francisco, CA 94134


Sunil Ojha, Ph.D.

Research Summary

My research focus is on the evolutionary relationship of enzymes that are dependent on cofactors, such as FAD, FMN, TPP and PLP dependent enzymes. I will be asking the following three questions:

  1. Within a family, do all the cofactor dependent enzymes utilize a common chemical strategy? To answer this question, I will analyze how enzymes interact with their cofactors. Within a family of related enzymes, I will compare cofactor-binding pockets to determine whether functional residues are conserved across the family. Conserved functional residues may be used to deduce the common mechanistic strategy employed by enzymes in the family.
  2. Does a cofactor impose constraints on the evolution of its protein partners? To answer this question, I will compare cofactor dependent enzymes to homologous enzymes that are not cofactor dependent.
  3. Can we predict whether ORFs of unknown function are cofactor dependent? Prediction of cofactor dependency for uncharacterized ORFs has previously been accomplished by searching for sequence homology to a motif or domain known to bind cofactor. However, searching for cofactor binding sites using only primary amino acid sequence yields numerous false positives, mainly because cofactor-binding residues may not be aligned linearly in the primary sequence. Consequently, I will utilize 3-dimentional structures of cofactor binding pockets to search structural databases for sequences that may be cofactor dependent.