Myoglobin (Mb), often referred to as the hydrogen atom of biology and a paradigm of complexity, has played a central role in research on the migration of gases, solvents, and ligands in the protein matrix. Despite the large number of details known about Mb dynamics, it still remains unclear how a ligand molecule escapes from the protein matrix to the solvent and how the protein matrix responds to the ligand migration at the atomic level. Scientists at KEK, along with other scientists from at Tokyo Institute of Technology, Yokohama City University, Nagoya University and Japan Science and Technology Agency have managed to visualize the dynamic and sequential structural deformation of internal cavities correlated with the ligand migration process in Mb.

Their novel method, continuous illumination on native MbCO crystals with pulsed laser at cryogenic temperatures, promoted slow CO migration even at 100K, and revealed that the migration of the CO molecule into each cavity induces expansion of the internal cavity itself. The sequential motion of the ligand and the cavity suggests a self-opening mechanism of the ligand migration channel arising from induced fit, which is further supported by computational geometry analysis. This result suggests a crucial role of the self-opening pathway model as a general mechanism of ligand migration in a protein matrix and will give further insights into the structure-based drug design.

This work has been published online in the Proceedings of the National Academy of Sciences online publication on February 9, 2009: Ayana Tomita, Tokushi Sato, Kouhei Ichiyanagi, Shunsuke Nozawa, Hirohiko Ichikawa, Matthieu Chollet, Fumihiro Kawai, Sam-Yong Park, Takayuki Tsuduki, Takahisa Yamato, Shin-ya Koshihara, and Shin-ichi Adachi, "Visualizing Breathing Motion of Internal Cavities in Concert with Ligand Migration in Myoglobin".
      http://www.pnas.org/content/early/2009/02/09/0807774106.full.pdf+htm

Figure 1  :  Myoglobin; the hydrogen atom of biology and a paradigm of complexity.

Figure 2  :  Schematic view of CO migration in myoglobin.

Figure 3  :  Electron densities and structural changes induced by laser excitation at 140K. Migration of CO molecule into each internal cavity induces expansion of the internal cavity itself.