STRUCTURE STABILITY IN THE ENOLASE SUPERFAMILY CATALYTIC MODULE

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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. In the enolase superfamily, a set of conserved active site residues (the "catalytic module") has repeatedly been used in nature in the evolution of many different enzymes for the performance of unique overall reactions involving a chemically diverse set of substrates. While these high-energy conformations of active site residues often destabilize the global stability of the enzyme through electrostatic or steric repulsion, results from several investigations have shown that this interplay is an essential element of enzyme catalysis, suggesting a stability trade-off for functionality. Structure solution and refinement of the o-succinylbenzoate synthase (OSBS) mutants show that the most conserved residues in the catalytic module (E190) is the most destabilizing, confirming the existence of the stability-functionality trade-off.