1r1x
From Proteopedia
(New page: 200px<br /> <applet load="1r1x" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r1x, resolution 2.15Å" /> '''Crystal structure o...) |
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==Overview== | ==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. | 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. | ||
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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: rochester]] | [[Category: rochester]] | ||
| - | ''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 18:58:36 2007'' |
Revision as of 16:52, 12 November 2007
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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 CMO, HEM and MBN 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 Mon Nov 12 18:58:36 2007
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
