3nml
Sperm whale myoglobin mutant H64W carbonmonoxy-form
Structural highlights
FunctionMYG_PHYMC Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHis(E7) to Trp replacements in HbA lead to markedly biphasic bimolecular CO rebinding after laser photolysis. For isolated mutant subunits, the fraction of fast phase increases with increasing [CO], suggesting a competition between binding to an open conformation with an empty E7 channel and relaxation to blocked or closed, slowly reacting states. The rate of conformational relaxation of the open state is ~18,000 s-1 in alpha subunits and ~10-fold faster in beta subunits, ~175,000 s-1. Crystal structures were determined for tetrameric alpha(wt)beta(Trp63) HbCO, alpha(Trp58)beta(wt) deoxyHb, and Trp64 deoxy- and CO-Mb as controls. In Trp63(E7) betaCO, the indole side chain is located in the solvent interface, blocking entry into the E7 channel. Similar blocked Trp64(E7) conformations are observed in the mutant Mb crystal structures. In Trp58(E7) deoxy-alpha subunits, the indole side chain fills both the channel and the distal pocket, forming a completely closed state. The bimolecular rate constant for CO binding, k'CO, to the open conformations of both mutant Hb subunits is ~80-90 uM-1s-1, whereas k'CO for the completely closed states is 1000-fold slower, ~0.08 uM-1s-1. A transient intermediate with k'CO approximately 0.7 uM-1s-1 is observed after photolysis of Trp63(E7) betaCO subunits and indicates that the indole ring blocks the entrance to the E7 channel, as observed in the crystal structures of Trp(E7) deoxyMb and betaCO subunits. Thus, either blocking or completely filling the E7 channel dramatically slows bimolecular binding, providing strong evidence that the E7 channel is the major pathway (>/= 90%) for ligand entry in human hemoglobin. Blocking the gate to ligand entry in human hemoglobin.,Birukou I, Soman J, Olson JS J Biol Chem. 2010 Dec 29. PMID:21193395[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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