1uiw
From Proteopedia
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| - | [[Image:1uiw.gif|left|200px]]<br /> | + | [[Image:1uiw.gif|left|200px]]<br /><applet load="1uiw" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1uiw" size=" | + | |
caption="1uiw, resolution 1.50Å" /> | caption="1uiw, resolution 1.50Å" /> | ||
'''Crystal Structures of Unliganded and Half-Liganded Human Hemoglobin Derivatives Cross-Linked between Lys 82beta1 and Lys 82beta2'''<br /> | '''Crystal Structures of Unliganded and Half-Liganded Human Hemoglobin Derivatives Cross-Linked between Lys 82beta1 and Lys 82beta2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A number of ligand binding studies of human adult hemoglobin (HbA) | + | A number of ligand binding studies of human adult hemoglobin (HbA) cross-linked between Lys 82beta(1) and Lys 82beta(2) with bis(3,5-dibromosalicyl)fumarate have been reported. The oxygen binding properties of native HbA, including the cooperativity and Bohr effect, are not substantially changed by the modification, provided care is taken to remove electrophoretically silent impurities arising from side reactions. We have refined the high-resolution structure of this modified Hb and found it adopts the T state when crystallized in the absence of heme ligands, contrary to a previously published structure. These results suggest the slightly altered crystal form determined previously may be due to unremoved side products of the cross-linking reaction with high oxygen affinity. Two nickel-substituted Hbs cross-linked in the same way have also been crystallized in the presence of carbon monoxide, which binds only to the ferrous heme. In the case of the nickel-substituted alpha subunit, the absence of a covalent link between the central metal of the heme and the proximal histidine leads to a new conformation of the histidine stabilized by a water molecule. This structure may mimic that of partially NO-liganded species of HbA; however, overall, the changes are highly localized, and both doubly ligated species are in the T conformation. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UIW 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 2FU as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1UIW 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=2FU:'>2FU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UIW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Park, S | + | [[Category: Park, S Y.]] |
[[Category: Shibayama, N.]] | [[Category: Shibayama, N.]] | ||
| - | [[Category: Tame, J | + | [[Category: Tame, J R.H.]] |
[[Category: 2FU]] | [[Category: 2FU]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
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[[Category: crystal structure]] | [[Category: crystal structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:24:59 2008'' |
Revision as of 13:24, 21 February 2008
|
Crystal Structures of Unliganded and Half-Liganded Human Hemoglobin Derivatives Cross-Linked between Lys 82beta1 and Lys 82beta2
Contents |
Overview
A number of ligand binding studies of human adult hemoglobin (HbA) cross-linked between Lys 82beta(1) and Lys 82beta(2) with bis(3,5-dibromosalicyl)fumarate have been reported. The oxygen binding properties of native HbA, including the cooperativity and Bohr effect, are not substantially changed by the modification, provided care is taken to remove electrophoretically silent impurities arising from side reactions. We have refined the high-resolution structure of this modified Hb and found it adopts the T state when crystallized in the absence of heme ligands, contrary to a previously published structure. These results suggest the slightly altered crystal form determined previously may be due to unremoved side products of the cross-linking reaction with high oxygen affinity. Two nickel-substituted Hbs cross-linked in the same way have also been crystallized in the presence of carbon monoxide, which binds only to the ferrous heme. In the case of the nickel-substituted alpha subunit, the absence of a covalent link between the central metal of the heme and the proximal histidine leads to a new conformation of the histidine stabilized by a water molecule. This structure may mimic that of partially NO-liganded species of HbA; however, overall, the changes are highly localized, and both doubly ligated species are in the T conformation.
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
1UIW is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structures of unliganded and half-liganded human hemoglobin derivatives cross-linked between Lys 82beta1 and Lys 82beta2., Park SY, Shibayama N, Hiraki T, Tame JR, Biochemistry. 2004 Jul 13;43(27):8711-7. PMID:15236579
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