W0129

Relation of Discrete Disorder to Function in Myoglobin. Martha Teeter, Chemistry, UC Davis and Boston College (Chestnut Hill, MA), One Shields Ave., Davis, CA 95616 USA.

Although myoglobin binds many ligands (O₂, CO, NO to name a few), the ligands can be stored in cavities and complex kinetics is found for different states of myoglobin. Photodissociation of ligands, mutagenesis, cryocrystallography and theoretical calculations suggest these cavities may be important not only to binding but enzymatic action of myoglobin. Ligands can migrate further into the protein via these cavities at different temperatures.

High resolution crystal structures (1.4 Å or higher) permit protein discrete disorder to be modeled. These form correlated clusters both on the protein surface and in its interior. Further, water chains with discrete disorder link these clusters. What is the role of discretely disordered residues in functional ligand migration in myoglobin?

Frauenfelder proposed a protein adopts an ensemble of states, like a glass. These are close in energy with low barriers between them. Such states are observed spectroscopically and correlate with discrete disorder of the distal His.

We studied the relation between multiple conformations and myoglobin dynamics and between multiple conformations and ligand migration in 1 Å structures of myoglobin. We find a key link that can aid in understanding a functional role for multiple conformations.