Download MendeleyR-state haemoglobin with low oxygen affinity: crystal structures of deoxy human and carbonmonoxy horse haemoglobin bound to the effector molecule L35
Yokoyama, T., Neya, S., Tsuneshige, A., Yonetani, T., Park, S.Y., Tame, J.R.(2006) J Mol Biol 356: 790-801
- PubMed: 16403522
- DOI: https://doi.org/10.1016/j.jmb.2005.12.018
- Primary Citation of Related Structures:
2D5X, 2D5Z, 2D60 - PubMed 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.
Organizational Affiliation:
Protein Design Laboratory, Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro, Tsurumi, Yokohama, 230-0045, Japan.
