Hemoglobin allosteric interactions

Heme—chemical models 307 Hemoglobin 289, 304-307 allosteric interactions 289-292, 302 Henderson-Hasselbalch equation 170 Heterotropic 290 Hexokinase 23, 51, 364 Hill constant 299, 300-302, 304 Hill equation 297 - 300 Hinge motions 48 HIV protease 486 Holoe nzyme 458 Homology 8, 9 Homology modeling 537 Homotropic 290 Hpr (histidine-containing... 

Figure 9 Two proposed models for allosteric interaction observed in hemoglobin, (a) A sequential model of allosteric interaction. When one O2 molecule binds to a subunit in the T-state, the subunit shifts to R-state and affects the affinity of neighboring subunits for the ligand binding, (b) An MWC two-state concerted model of allosteric interaction. When one O2 molecule binds to a subunit in all T-states, a concerted conformational change occurs to produce a protein with all R-state subimits. Square and circle represent T- and R-state subunits, respectively. Moreover, opened and closed diagrams represent free and O2 bound subunits, respectively...

Finally, in proteins with multiple binding sites e.g. transferrin), or in complex protein assemblies with multiple subunits e.g. hemoglobin) there is an opportunity for allosteric interactions between redox-active iron sites. These allosteric interactions are readily probed by the spectroelectrochemical technique, as illustrated in Sections 2.3.2.2 and 2.4.2.3. 

In hemoglobin, the interactions between the subunits are known under the general term of allosteric properties and are of great physiological importance. They determine the cooperative binding of O2. In the deoxy form, the iron atom of each heme is in a high-spin (S =2) five-coordinate iron(II) state and lies about 0.5 A out of the heme plane in the direction of the proximal histidine [12]. The Fe-N(imida2ole) bond vector has 10° tilt off the heme normal. 

A similar system has been used to study the influence of allosteric interactions on cyanide dissociation in hemoglobin (112). The results of these RSSF studies demonstrate that the cyanide complex of the a- and 3-chains are spectroscopically distinguishable and that dissociation is a cooperative process that is modulated by allosteric effectors. 

Bonaventura, J., Bonaventura, C., Amiconi, G., Tentori, L., Brunori, M., and Antonini, E., 1975, Allosteric interactions in non-a chains isolated from normal human hemoglobin, fetal hemoglobin, and hemoglobin Abruzzo (j8 143(H21) His —> Arg), /. Biol. Chem. 250 6278. 

The interactions between the allosteric effectors and hemoglobin add hydrogen bonds to the Hb tense state, similar to DPG, and therefore stabilize that state, resulting in an increased delivery of oxygen. 

STEREOCHEMICAL TERMINOLOGY, lUPAC RECOMMENDATIONS HOMOTROPIC INTERACTION MONOD-WYMAN-CHANGEUX MODEL ALLOSTERISM HEMOGLOBIN "HONDO,"... 

The term "quaternary structure" refers to the interaction of several polypeptide chains in a noncovalent manner to form multisubunit protein particles termed oligomers. Individual subunit polypeptide chains are also referred to as protomers. Oligomers usually have an even number of subunits (two or more). The noncovalent interactions may be of the hydrophobic, hydrogen bond, or the polar type. Examples are hemoglobin and lactate dehydrogenase (four protomers each) and many allosteric enzymes. 

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