1f65
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CRYSTAL STRUCTURE OF OXY SPERM WHALE MYOGLOBIN MUTANT Y(B10)Q(E7)R(E10)
OverviewOverview
A triple mutant of sperm whale myoglobin (Mb) [Leu(B10) --> Tyr, His(E7), --> Gln, and Thr(E10) --> Arg, called Mb-YQR], investigated by, stopped-flow, laser photolysis, crystallography, and molecular dynamics, (MD) simulations, proved to be quite unusual. Rebinding of, photodissociated NO, O2, and CO from within the protein (in a "geminate", mode) allows us to reach general conclusions about dynamics and cavities, in proteins. The 3D structure of oxy Mb-YQR shows that bound O2 makes two, H-bonds with Tyr(B10)29 and Gln(E7)64; on deoxygenation, these two, residues move toward the space occupied by O2. The bimolecular rate, constant for NO binding is the same as for wild-type, but those for CO and, O2 binding are reduced 10-fold. While there is no geminate recombination, with O2 and CO, geminate rebinding of NO displays an unusually large and, very slow component, which is pretty much abolished in the presence of, xenon. These results and MD simulations suggest that the ligand migrates, in the protein matrix to a major "secondary site," located beneath, Tyr(B10)29 and accessible via the motion of Ile(G8)107; this site is, different from the "primary site" identified by others who investigated, the photolyzed state of wild-type Mb by crystallography. Our hypothesis, may rationalize the O2 binding properties of Mb-YQR, and more generally to, propose a mechanism of control of ligand binding and dissociation in, hemeproteins based on the dynamics of side chains that may (or may not), allow access to and direct temporary sequestration of the dissociated, ligand in a docking site within the protein. This interpretation suggests, that very fast (picosecond) fluctuations of amino acid side chains may, play a crucial role in controlling O2 delivery to tissue at a rate, compatible with physiology.
About this StructureAbout this Structure
1F65 is a Single protein structure of sequence from Physeter catodon with SO4, HEM and OXY as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structural dynamics of ligand diffusion in the protein matrix: A study on a new myoglobin mutant Y(B10) Q(E7) R(E10)., Brunori M, Cutruzzola F, Savino C, Travaglini-Allocatelli C, Vallone B, Gibson QH, Biophys J. 1999 Mar;76(3):1259-69. PMID:10049310
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