2d60: Difference between revisions
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[[Image:2d60.gif|left|200px]]<br /> | [[Image:2d60.gif|left|200px]]<br /><applet load="2d60" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2d60" size=" | |||
caption="2d60, resolution 1.70Å" /> | caption="2d60, resolution 1.70Å" /> | ||
'''Crystal structure of deoxy human hemoglobin complexed with two L35 molecules'''<br /> | '''Crystal structure of deoxy human hemoglobin complexed with two L35 molecules'''<br /> | ||
==Overview== | ==Overview== | ||
Although detailed crystal structures of haemoglobin (Hb) provide a clear | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2D60 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HEM and L35 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2D60 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=L35:'>L35</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D60 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Neya, S.]] | [[Category: Neya, S.]] | ||
[[Category: Park, S | [[Category: Park, S Y.]] | ||
[[Category: Tame, J | [[Category: Tame, J R.]] | ||
[[Category: Tsuneshige, A.]] | [[Category: Tsuneshige, A.]] | ||
[[Category: Yokoyama, T.]] | [[Category: Yokoyama, T.]] | ||
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[[Category: l35]] | [[Category: l35]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:55:40 2008'' | ||
Revision as of 17:55, 21 February 2008
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Crystal structure of deoxy human hemoglobin complexed with two L35 molecules
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 and 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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