1i3d: Difference between revisions
New page: left|200px<br /> <applet load="1i3d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i3d, resolution 1.70Å" /> '''HUMAN CARBONMONOXY ... |
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==Overview== | ==Overview== | ||
Hemoglobin (Hb) Bart's is present in the red blood cells of millions of, people worldwide who suffer from alpha-thalassemia. alpha-Thalassemia is a, disease in which there is a deletion of one or more of the four, alpha-chain genes, and excess gamma and beta chains spontaneously form, homotetramers. The gamma(4) homotetrameric protein known as Hb Bart's is a, stable species that exhibits neither a Bohr effect nor heme-heme, cooperativity. Although Hb Bart's has a higher O(2) affinity than either, adult (alpha(2)beta(2)) or fetal (alpha(2)gamma(2)) Hbs, it has a lower, affinity for O(2) than HbH (beta(4)). To better understand the association, and ligand binding properties of the gamma(4) tetramer, we have solved the, structure of Hb Bart's in two different oxidation and ligation states. The, crystal structure of ferrous carbonmonoxy (CO) Hb Bart's was determined by, molecular replacement and refined at 1.7 A resolution (R = 21.1%, R(free), = 24.4%), and that of ferric azide (N(3)(-)) Hb Bart's was similarly, determined at 1.86 A resolution (R = 18.4%, R(free) = 22.0%). In the, carbonmonoxy-Hb structure, the CO ligand is bound at an angle of 140, degrees, and with an unusually long Fe-C bond of 2.25 A. This geometry is, attributed to repulsion from the distal His63 at the low pH of, crystallization (4.5). In contrast, azide is bound to the oxidized heme, iron in the methemoglobin crystals at an angle of 112 degrees, in a, perfect orientation to accept a hydrogen bond from His63. Compared to the, three known quaternary structures of human Hb (T, R, and R2), both, structures most closely resemble the R state. Comparisons with the, structures of adult Hb and HbH explain the association and dissociation, behaviour of Hb homotetramers relative to the heterotetrameric Hbs. | Hemoglobin (Hb) Bart's is present in the red blood cells of millions of, people worldwide who suffer from alpha-thalassemia. alpha-Thalassemia is a, disease in which there is a deletion of one or more of the four, alpha-chain genes, and excess gamma and beta chains spontaneously form, homotetramers. The gamma(4) homotetrameric protein known as Hb Bart's is a, stable species that exhibits neither a Bohr effect nor heme-heme, cooperativity. Although Hb Bart's has a higher O(2) affinity than either, adult (alpha(2)beta(2)) or fetal (alpha(2)gamma(2)) Hbs, it has a lower, affinity for O(2) than HbH (beta(4)). To better understand the association, and ligand binding properties of the gamma(4) tetramer, we have solved the, structure of Hb Bart's in two different oxidation and ligation states. The, crystal structure of ferrous carbonmonoxy (CO) Hb Bart's was determined by, molecular replacement and refined at 1.7 A resolution (R = 21.1%, R(free), = 24.4%), and that of ferric azide (N(3)(-)) Hb Bart's was similarly, determined at 1.86 A resolution (R = 18.4%, R(free) = 22.0%). In the, carbonmonoxy-Hb structure, the CO ligand is bound at an angle of 140, degrees, and with an unusually long Fe-C bond of 2.25 A. This geometry is, attributed to repulsion from the distal His63 at the low pH of, crystallization (4.5). In contrast, azide is bound to the oxidized heme, iron in the methemoglobin crystals at an angle of 112 degrees, in a, perfect orientation to accept a hydrogen bond from His63. Compared to the, three known quaternary structures of human Hb (T, R, and R2), both, structures most closely resemble the R state. Comparisons with the, structures of adult Hb and HbH explain the association and dissociation, behaviour of Hb homotetramers relative to the heterotetrameric Hbs. | ||
==Disease== | |||
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]], LADD syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: oxygen transport]] | [[Category: oxygen transport]] | ||
''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 17:25:42 2007'' | ||
Revision as of 18:19, 12 November 2007
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HUMAN CARBONMONOXY HEMOGLOBIN BART'S (GAMMA4)
OverviewOverview
Hemoglobin (Hb) Bart's is present in the red blood cells of millions of, people worldwide who suffer from alpha-thalassemia. alpha-Thalassemia is a, disease in which there is a deletion of one or more of the four, alpha-chain genes, and excess gamma and beta chains spontaneously form, homotetramers. The gamma(4) homotetrameric protein known as Hb Bart's is a, stable species that exhibits neither a Bohr effect nor heme-heme, cooperativity. Although Hb Bart's has a higher O(2) affinity than either, adult (alpha(2)beta(2)) or fetal (alpha(2)gamma(2)) Hbs, it has a lower, affinity for O(2) than HbH (beta(4)). To better understand the association, and ligand binding properties of the gamma(4) tetramer, we have solved the, structure of Hb Bart's in two different oxidation and ligation states. The, crystal structure of ferrous carbonmonoxy (CO) Hb Bart's was determined by, molecular replacement and refined at 1.7 A resolution (R = 21.1%, R(free), = 24.4%), and that of ferric azide (N(3)(-)) Hb Bart's was similarly, determined at 1.86 A resolution (R = 18.4%, R(free) = 22.0%). In the, carbonmonoxy-Hb structure, the CO ligand is bound at an angle of 140, degrees, and with an unusually long Fe-C bond of 2.25 A. This geometry is, attributed to repulsion from the distal His63 at the low pH of, crystallization (4.5). In contrast, azide is bound to the oxidized heme, iron in the methemoglobin crystals at an angle of 112 degrees, in a, perfect orientation to accept a hydrogen bond from His63. Compared to the, three known quaternary structures of human Hb (T, R, and R2), both, structures most closely resemble the R state. Comparisons with the, structures of adult Hb and HbH explain the association and dissociation, behaviour of Hb homotetramers relative to the heterotetrameric Hbs.
DiseaseDisease
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[602115], LADD syndrome OMIM:[602115]
About this StructureAbout this Structure
1I3D is a Single protein structure of sequence from Homo sapiens with HEM and CMO as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Oligomerization and ligand binding in a homotetrameric hemoglobin: two high-resolution crystal structures of hemoglobin Bart's (gamma(4)), a marker for alpha-thalassemia., Kidd RD, Baker HM, Mathews AJ, Brittain T, Baker EN, Protein Sci. 2001 Sep;10(9):1739-49. PMID:11514664
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