Positive cooperativity induces multimodal site and thermodynamic affinity distributions in multivalent proteins.
The characterization of the stoichiometric and site-affinity distributions for the reaction of hemoglobin with O(2) and CO is presented as an example of a multivalent receptor system which exhibits positive site-site interactions. The distributions of stoichiometric constants, T(i)(K(i))'s, are obtained assuming that the distribution of site constants, N(k), is known. The importance of these distributions is that they can be directly related to quantities measured experimentally and that they represent affinity distributions for each ligation step. In hemoglobin, positive site-site interactions generate both stoichiometric and site-affinity distributions with complex and previously unrecognized multimodal patterns that are very different from the theoretical distributions obtained in the absence of interactions. These distributions are related to the generation of heterogeneity during the ligand binding process. Experimental binding data show that these complex distributions can be related to the physiological functions of uptake, transport, and release of gaseous ligands by hemoglobin.
del Mar Hernández
María
M
Grupo de Biología Teórica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, Ciudad Universitaria, 04510 México D.F., Mexico.
José
Marco V
MV
D001665:Binding Sites; D002248:Carbon Monoxide / Q000737:chemistry / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D008956:Models, Chemical; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010313:Partial Pressure; D011485:Protein Binding; D013816:Thermodynamics
D006454:Hemoglobins; D008024:Ligands; D002248:Carbon Monoxide; D010100:Oxygen