AI Article Synopsis

  • Crystal structures of hemoglobin show how it controls oxygen binding, but new artificial effector molecules provide even greater control than natural compounds.
  • One such compound, bezafibrate (BZF), binds to hemoglobin's alpha subunits, lowering its oxygen affinity without changing it to the tense state.
  • A related compound, L35, binds to the central cavity of both R and T state hemoglobin, and the study explores how this affects oxygen affinity based on recent spectroscopic findings.

Article Abstract

Although detailed crystal structures of haemoglobin (Hb) provide a clear understanding of the basic allosteric mechanism of the protein, and how this in turn controls oxygen affinity, recent experiments with artificial effector molecules have shown a far greater control of oxygen binding than with natural heterotropic effectors. Contrary to the established text-book view, these non-physiological compounds are able to reduce oxygen affinity very strongly without switching the protein to the T (tense) state. In an earlier paper we showed that bezafibrate (BZF) binds to a surface pocket on the alpha subunits of R state Hb, strongly reducing the oxygen affinity of this protein conformation. Here we report the crystallisation of Hb with L35, a related compound, and show that this binds to the central cavity of both R and T state Hb. The mechanism by which L35 reduces oxygen affinity is discussed, in relation to spectroscopic studies of effector binding.

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http://dx.doi.org/10.1016/j.jmb.2005.12.018DOI Listing

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