2d60
Crystal structure of deoxy human hemoglobin complexed with two L35 molecules
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OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Erythremias, alpha- OMIM:[141800], Erythremias, beta- OMIM:[141900], Erythrocytosis OMIM:[141850], HPFH, deletion type OMIM:[141900], Heinz body anemia OMIM:[141850], Heinz body anemias, alpha- OMIM:[141800], Heinz body anemias, beta- OMIM:[141900], Hemoglobin H disease OMIM:[141850], Hypochromic microcytic anemia OMIM:[141850], Methemoglobinemias, alpha- OMIM:[141800], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia, alpha- OMIM:[141850], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, alpha- OMIM:[141800], Thalassemias, beta- OMIM:[141900]
About this StructureAbout this Structure
2D60 is a Protein complex structure of sequences from Homo sapiens with HEM and L35 as ligands. Full crystallographic information is available from OCA.
ReferenceReference
R-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 SY, Tame JR, J Mol Biol. 2006 Feb 24;356(3):790-801. Epub 2005 Dec 21. PMID:16403522
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