This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to determine the structural basis of catalytic promiscuity in the enzyme o-Succinylbenzoate synthase (OSBS), a member of the enolase superfamily. Members of the OSBS family can share as little as 15% identity, and the only conserved residues in the family are also conserved in other members of the enolase superfamily which catalyze different reactions. This suggests that although OSBS function has been maintained during the course of evolution, the residues and structures that determine this function have evolved divergently and are not conserved. We are determining the structural basis for OSBS catalysis by using structural comparisons to rationally design mutations that are predicted to affect OSBS activity. In addition, many members of one branch of the OSBS family catalyze a second reaction, N-succinylamino acid racemization (NSAR). We are performing structural, phylogenetic, and mutagenesis studies to determine how some members of the OSBS family can catalyze the NSAR reaction while others cannot. This project will utilize several RBVI resources, including Chimera, the Structure Function Linkage Database, and software available through RBVI such as GCG and MrBayes. Comparing structures, function and evolution of the OSBS family will add to our understanding about the functional plasticity of proteins and how structure mediates function.
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