2d60
From Proteopedia
(New page: 200px<br /> <applet load="2d60" size="450" color="white" frame="true" align="right" spinBox="true" caption="2d60, resolution 1.70Å" /> '''Crystal structure o...) |
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==Overview== | ==Overview== | ||
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. | 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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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Erythremias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Erythremias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Erythrocytosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], HPFH, deletion type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Heinz body anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Heinz body anemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Heinz body anemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Hemoglobin H disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Hypochromic microcytic anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Methemoglobinemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Methemoglobinemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Sickle cell anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Thalassemia, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Thalassemia-beta, dominant inclusion-body OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Thalassemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Thalassemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: l35]] | [[Category: l35]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:26:32 2007'' |
Revision as of 19:20, 12 November 2007
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Crystal structure of deoxy human hemoglobin complexed with two L35 molecules
Contents |
Overview
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
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 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.
Reference
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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