1r1x
From Proteopedia
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| - | [[Image:1r1x.gif|left|200px]]<br /> | + | [[Image:1r1x.gif|left|200px]]<br /><applet load="1r1x" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1r1x" size=" | + | |
caption="1r1x, resolution 2.15Å" /> | caption="1r1x, resolution 2.15Å" /> | ||
'''Crystal structure of oxy-human hemoglobin Bassett at 2.15 angstrom'''<br /> | '''Crystal structure of oxy-human hemoglobin Bassett at 2.15 angstrom'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Hemoglobin (Hb) Bassett, an abnormal Hb variant with a markedly reduced | + | Hemoglobin (Hb) Bassett, an abnormal Hb variant with a markedly reduced oxygen affinity, was discovered in a Caucasian (Anglo-Saxon) male child who experienced episodes of cyanosis. Cation-exchange and reversed-phase (RP) high-performance liquid chromatography (HPLC) showed that the patient has an abnormal Hb, with a mutation in the alpha-globin. Tryptic peptide digest of the abnormal alpha-globin with subsequent HPLC analysis revealed abnormal elution of the alpha-T11 peptide. Further studies with Edman sequencing and electrospray mass spectrometry of tryptic peptide alpha-T11, as well as structural analysis by X-ray crystallography revealed an Asp-->Ala substitution at the alpha94 (G1) position, a match for Hb Bassett. Detailed functional studies showed that this Hb variant had a markedly reduced oxygen affinity (P(50) at pH 7.0 = 22 mmHg; Hb A P(50) = 10.5 mmHg), reduced Bohr effect (-0.26 compared to - 0.54 in Hb A), and low subunit cooperativity (n = 1.4, compared to 2.6 in Hb A). X-ray crystallography results explain the probable effects of the structural modification on the oxygen-binding properties of this Hb variant. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1R1X 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 CMO, HEM and MBN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1R1X 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=CMO:'>CMO</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=MBN:'>MBN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R1X OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Abdulmalik, O.]] | [[Category: Abdulmalik, O.]] | ||
| - | [[Category: Abraham, D | + | [[Category: Abraham, D J.]] |
[[Category: Asakura, T.]] | [[Category: Asakura, T.]] | ||
[[Category: Dhaikin, Y.]] | [[Category: Dhaikin, Y.]] | ||
| - | [[Category: Lerner, N | + | [[Category: Lerner, N B.]] |
[[Category: Ochotorena, J.]] | [[Category: Ochotorena, J.]] | ||
| - | [[Category: Safo, M | + | [[Category: Safo, M K.]] |
[[Category: CMO]] | [[Category: CMO]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
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[[Category: rochester]] | [[Category: rochester]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:46:08 2008'' |
Revision as of 12:46, 21 February 2008
|
Crystal structure of oxy-human hemoglobin Bassett at 2.15 angstrom
Contents |
Overview
Hemoglobin (Hb) Bassett, an abnormal Hb variant with a markedly reduced oxygen affinity, was discovered in a Caucasian (Anglo-Saxon) male child who experienced episodes of cyanosis. Cation-exchange and reversed-phase (RP) high-performance liquid chromatography (HPLC) showed that the patient has an abnormal Hb, with a mutation in the alpha-globin. Tryptic peptide digest of the abnormal alpha-globin with subsequent HPLC analysis revealed abnormal elution of the alpha-T11 peptide. Further studies with Edman sequencing and electrospray mass spectrometry of tryptic peptide alpha-T11, as well as structural analysis by X-ray crystallography revealed an Asp-->Ala substitution at the alpha94 (G1) position, a match for Hb Bassett. Detailed functional studies showed that this Hb variant had a markedly reduced oxygen affinity (P(50) at pH 7.0 = 22 mmHg; Hb A P(50) = 10.5 mmHg), reduced Bohr effect (-0.26 compared to - 0.54 in Hb A), and low subunit cooperativity (n = 1.4, compared to 2.6 in Hb A). X-ray crystallography results explain the probable effects of the structural modification on the oxygen-binding properties of this Hb variant.
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
1R1X is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Characterization of hemoglobin bassett (alpha94Asp-->Ala), a variant with very low oxygen affinity., Abdulmalik O, Safo MK, Lerner NB, Ochotorena J, Daikhin E, Lakka V, Santacroce R, Abraham DJ, Asakura T, Am J Hematol. 2004 Nov;77(3):268-76. PMID:15495251
Page seeded by OCA on Thu Feb 21 14:46:08 2008
Categories: Homo sapiens | Protein complex | Abdulmalik, O. | Abraham, D J. | Asakura, T. | Dhaikin, Y. | Lerner, N B. | Ochotorena, J. | Safo, M K. | CMO | HEM | MBN | Carbon monoxide | Crystal structure | Hemoglobin | Mutant | Oxygen affinity | Rochester
