Data di Pubblicazione:
2006
Citazione:
Crucial role of ligation analogues in the understanding of hemoglobin cooperativity / M. Perrella, R. Russo. - In: ATTI DELLA ACCADEMIA NAZIONALE DEI LINCEI. RENDICONTI LINCEI. SCIENZE FISICHE E NATURALI. - ISSN 1120-6349. - serie 9, vol.17:1-2(2006), pp. 163-181. ((Intervento presentato al convegno Allosteric Proteins : 40 years with Monod-Wyman-Changeaux tenutosi a Roma nel 2005 [10.1007/BF02904507].
Abstract:
The functional/structural analysis of the ligation intermediates is the most powerful approach to the study of hemoglobin cooperativity. Carbon monoxide is as cooperative as O2 in the interaction with hemoglobin and the distributions of its ligation intermediates under equilibrium and dynamic conditions have been experimentally determined using cryogenic techniques. The analyses of such distributions have contributed to test theoretical models of cooperativity. However, conclusive evidence on the mechanisms of cooperativity requires the direct study of the functional properties of specific intermediates, which is not possible using O2 or CO. Ligation analogues, such as the complex of cyanide with the heme in the ferric state and the metal substituted hemoglobins, are indispensable tools for cooperativity studies provided that O2, CO and other ligation analogues share the same basic mechanisms. We have shown that this is true for CO and the cyanomet ligation analogue. This finding adds significance to our studies of the Bohr effects of the cyanomet ligation intermediates. In this paper we review our work on the CO and cyanomet intermediates. The conclusion drawn from such studies is that the basic mechanism of hemoglobin cooperativity contains elements of both the concerted and sequential models. The interaction of one ligand molecule with deoxy hemoglobin does not promote an equilibrium between T and R quaternary structures. A T→R switch seems to occur upon binding the second ligand molecule. However, a definite statement in this regard cannot be made until the problem of the thermodynamic equivalence of the diliganded intermediates is definitely clarified. Lastly, the tertiary structures of the unliganded subunits in the R and T structures are functionally different.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
M. Perrella, R. Russo
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