Myoglobin

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Myoglobin
Model of helical domains in myoglobin.[1]
Available structures
1m6c, 1m6m, 1mdn, 1mnh, 1mni, 1mnj, 1mnk, 1mno, 1mwc, 1mwd, 1myg, 1myh, 1myi, 1myj, 1pmb, 1yca, 1ycb, 2mm1
Identifiers
Symbols	MB; MGC13548; PVALB
External IDs	OMIM: 160000 MGI: 96922 HomoloGene: 3916
Gene ontology Molecular function • oxygen transporter activity • iron ion binding • oxygen binding • heme binding • metal ion binding Biological process • response to hypoxia • transport • oxygen transport • enucleate erythrocyte differentiation
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4151	17189
Ensembl	ENSG00000198125	ENSMUSG00000018893
UniProt	P02144	Q3UVB1
RefSeq	NM_005368 (mRNA)	NM_013593 (mRNA)
	NP_005359 (protein)	NP_038621 (protein)
Location	Chr 22: 34.33 - 34.35 Mb	Chr 15: 76.84 - 76.88 Mb
PubMed search	[1]	[2]

Myoglobin is a protein that in humans is encoded by the MB gene.^[2]

Myoglobin is a single-chain globular protein of 153 amino acids, containing a heme (iron-containing porphyrin) prosthetic group in the center around which the remaining apoprotein folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 16,700 daltons, and is the primary oxygen-carrying pigment of muscle tissues.^[3] Unlike the blood-borne hemoglobin, to which it is structurally related,^[4] this protein does not exhibit cooperative binding of oxygen, since positive cooperativity is a property of multimeric/oligomeric proteins only. Instead, the binding of oxygen by myoglobin is unaffected by the oxygen pressure in the surrounding tissue. Myoglobin is often cited as having an "instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation curve. High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer.

In 1958, John Kendrew and associates successfully determined the structure of myoglobin by high-resolution X-ray crystallography.^[5] For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.^[6] Despite being one of the most studied proteins in biology, its true physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin are viable, but showed a 30% reduction in cardiac systolic output. They adapted to this deficiency through hypoxic genetic mechanisms and increased vasodilation.^[7]

[edit] Meat color

An X-ray diffraction image for the protein myoglobin.

Myoglobin forms pigments responsible for making meat red. The color that meat takes is partly determined by the charge of the iron atom in myoglobin and the oxygen attached to it. When meat is in its raw state, the iron atom is in the +2 oxidation state, and is bound to a dioxygen molecule (O₂). Meat cooked well done is brown because the iron atom is now in the +3 oxidation state, having lost an electron, and is now coordinated by a water molecule. Under some conditions, meat can also remain pink all through cooking, despite being heated to high temperatures. If meat has been exposed to nitrites, it will remain pink because the iron atom is bound to NO, nitric oxide (true of, e.g., corned beef or cured hams). Grilled meats can also take on a pink "smoke ring" that comes from the iron binding a molecule of carbon monoxide to give metmyoglobin.^[8] Raw meat packed in a carbon monoxide atmosphere also shows this same pink "smoke ring" due to the same coordination chemistry. Notably, the surface of the raw meat also displays the pink color, which is usually associated in consumers' minds with fresh meat. This artificially-induced pink color can persist in the meat for a very long time, reportedly up to one year. ^[9] Hormel and Cargill are both reported to use this meat-packing process, and meat treated this way has been in the consumer market since 2003.^[10] Myoglobin is found in Type I muscle, Type II A and Type II B, but most texts consider myoglobin not to be found in smooth muscle.

[edit] Role in disease

Myoglobin is released from damaged muscle tissue (rhabdomyolysis), which has very high concentrations of myoglobin. The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute renal failure.^[11]

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain.^[12] CK-MB and cTnT is used in combination with ECG, and the clinical signs to diagnose Acute Myocardial Infarction (AMI).

[edit] Structure and bonding

Myoglobin contains a porphyrin ring with an iron center. There is a proximal histidine group attached directly to the iron center, and a distal histidine group on the opposite face, not bonded to the iron.

Many functional models of myoglobin have been studied. One of the most important is that of picket fence porphyrin by James Collman. This model was used to show the importance of the distal prosthetic group. It serves three functions:

1. To form hydrogen bonds with the dioxygen moiety, increasing the O₂ binding constant
2. To prevent the binding of carbon monoxide, whether from within or without the body. Carbon monoxide binds to iron in an end-on fashion, and is hindered by the presence of the distal histidine, which forces it into a bent conformation. CO binds to heme 23,000 times better than O₂, but only 200 times better in hemoglobin and myoglobin. Oxygen binds in a bent fashion, which can fit with the distal histidine.^[13]
3. To prevent irreversible dimerization of the oxymyoglobin with another deoxymyoglobin species

[edit] See also

• Hemoglobin
• Neuroglobin
• Cytoglobin
• Hemoprotein

[edit] References

[edit] Further reading

[edit] External links

• The Myoglobin Protein
• Protein Database featured molecule
• Online 'Mendelian Inheritance in Man' (OMIM) 160000 human genetics
• Which Cut Is Older? (It's a Trick Question) New York Times, February 21, 2006 article regarding meat industry use of carbon monoxide to keep meat looking red.
• Stores React to Meat Reports New York Times, March 1, 2006 article on the use of carbon monoxide to make meat appear fresh.

v • d • e PDB Gallery 1m6c: V68N MYOGLOBIN WITH CO   1m6m: V68N MET MYOGLOBIN   1mdn: WILD TYPE MYOGLOBIN WITH CO   1mnh: INTERACTIONS AMONG RESIDUES CD3, E7, E10 AND E11 IN MYOGLOBINS: ATTEMPTS TO SIMULATE THE O2 AND CO BINDING PROPERTIES OF APLYSIA MYOGLOBIN   1mni: ALTERATION OF AXIAL COORDINATION BY PROTEIN ENGINEERING IN MYOGLOBIN. BIS-IMIDAZOLE LIGATION IN THE HIS64-->VAL(SLASH)VAL68-->HIS DOUBLE MUTANT   1mnj: INTERACTIONS AMONG RESIDUES CD3, E7, E10 AND E11 IN MYOGLOBINS: ATTEMPTS TO SIMULATE THE O2 AND CO BINDING PROPERTIES OF APLYSIA MYOGLOBIN   1mnk: INTERACTIONS AMONG RESIDUES CD3, E7, E10 AND E11 IN MYOGLOBINS: ATTEMPTS TO SIMULATE THE O2 AND CO BINDING PROPERTIES OF APLYSIA MYOGLOBIN   1mno: V68N MYOGLOBIN OXY FORM   1mwc: WILD TYPE MYOGLOBIN WITH CO   1mwd: WILD TYPE DEOXY MYOGLOBIN   1myg: HIGH RESOLUTION X-RAY STRUCTURES OF PIG METMYOGLOBIN AND TWO CD3 MUTANTS MB(LYS45-> ARG) AND MB(LYS45-> SER)   1myh: HIGH RESOLUTION X-RAY STRUCTURES OF PIG METMYOGLOBIN AND TWO CD3 MUTANTS MB(LYS45-> ARG) AND MB(LYS45-> SER)   1myi: HIGH RESOLUTION X-RAY STRUCTURES OF PIG METMYOGLOBIN AND TWO CD3 MUTANTS MB(LYS45-> ARG) AND MB(LYS45-> SER)   1myj: DISTAL POLARITY IN LIGAND BINDING TO MYOGLOBIN: STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF A THREONINE68(E11) MUTANT   1pmb: THE DETERMINATION OF THE CRYSTAL STRUCTURE OF RECOMBINANT PIG MYOGLOBIN BY MOLECULAR REPLACEMENT AND ITS REFINEMENT   1yca: DISTAL POCKET POLARITY IN LIGAND BINDING TO MYOGLOBIN: DEOXY AND CARBONMONOXY FORMS OF A THREONINE68 (E11) MUTANT INVESTIGATED BY X-RAY CRYSTALLOGRAPHY AND INFRARED SPECTROSCOPY   1ycb: DISTAL POCKET POLARITY IN LIGAND BINDING TO MYOGLOBIN: DEOXY AND CARBONMONOXY FORMS OF A THREONINE68 (E11) MUTANT INVESTIGATED BY X-RAY CRYSTALLOGRAPHY AND INFRARED SPECTROSCOPY   2mm1: X-RAY CRYSTAL STRUCTURE OF A RECOMBINANT HUMAN MYOGLOBIN MUTANT AT 2.8 ANGSTROMS RESOLUTION