Tunnels from heme pocket to the outside of protein. Possible tunnels from heme pocket to the outside of protein are estimated with the program CAVER (37). Upper and lower panels show unbound (PDB ID: 1UBB) and CO-bound forms (PDB ID: 1IX4), respectively (16). Heme, Met-51, Asp-140, Gln-145, and Phe-167 are shown as orange stick model. Top 5 tunnels in unbound and CO-bound forms are shown. Some tunnel formations are depending on the conformation change upon CO binding. In unbound form, one tunnel through the site-3 and γ- meso side of heme is formed, on the other hands, another tunnel from the site-2 and the α-meso side of heme is formed in CO-bound form.