1dxv: Difference between revisions
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==Overview== | ==Overview== | ||
The crystal structures of three mutant hemoglobins reconstituted from, recombinant beta chains and authentic human alpha chains have been, determined in the deoxy state at 1.8-A resolution. The primary structures, of the mutant hemoglobins differ at the beta-chain amino terminus. One, mutant, beta Met, is characterized by the addition of a methionine at the, amino terminus. The other two hemoglobins are characterized by, substitution of Val 1 beta with either a methionine, beta V1M, or an, alanine, beta V1A. All the mutation-induced structural perturbations are, small intrasubunit changes that are localized to the immediate vicinity of, the beta-chain amino terminus. In the beta Met and beta V1A mutants, the, mobility of the beta-chain amino terminus increases and the electron, density of an associated inorganic anion is decreased. In contrast, the, beta-chain amino terminus of the beta V1M mutant becomes less mobile, and, the inorganic anion binds with increased affinity. These structural, differences can be correlated with functional data for the mutant, hemoglobins [Doyle, M. L., Lew, G., DeYoung, A., Kwiatkowski, L., Noble, R. W., & Ackers, G. K. (1992) Biochemistry preceding paper is this issue], as well as with the properties of ruminant hemoglobins and a mechanism, [Perutz, M., & Imai, K. (1980) J. Mol. Biol. 136, 183-191] that relates, the intrasubunit interactions of the beta-chain amino terminus to changes, in oxygen affinity. Since the structures of the mutant deoxyhemoglobins, show only subtle differences from the structure of deoxyhemoglobin A, it, is concluded that any of the three hemoglobins could probably function as, a surrogate for hemoglobin A.(ABSTRACT TRUNCATED AT 250 WORDS) | The crystal structures of three mutant hemoglobins reconstituted from, recombinant beta chains and authentic human alpha chains have been, determined in the deoxy state at 1.8-A resolution. The primary structures, of the mutant hemoglobins differ at the beta-chain amino terminus. One, mutant, beta Met, is characterized by the addition of a methionine at the, amino terminus. The other two hemoglobins are characterized by, substitution of Val 1 beta with either a methionine, beta V1M, or an, alanine, beta V1A. All the mutation-induced structural perturbations are, small intrasubunit changes that are localized to the immediate vicinity of, the beta-chain amino terminus. In the beta Met and beta V1A mutants, the, mobility of the beta-chain amino terminus increases and the electron, density of an associated inorganic anion is decreased. In contrast, the, beta-chain amino terminus of the beta V1M mutant becomes less mobile, and, the inorganic anion binds with increased affinity. These structural, differences can be correlated with functional data for the mutant, hemoglobins [Doyle, M. L., Lew, G., DeYoung, A., Kwiatkowski, L., Noble, R. W., & Ackers, G. K. (1992) Biochemistry preceding paper is this issue], as well as with the properties of ruminant hemoglobins and a mechanism, [Perutz, M., & Imai, K. (1980) J. Mol. Biol. 136, 183-191] that relates, the intrasubunit interactions of the beta-chain amino terminus to changes, in oxygen affinity. Since the structures of the mutant deoxyhemoglobins, show only subtle differences from the structure of deoxyhemoglobin A, it, is concluded that any of the three hemoglobins could probably function as, a surrogate for hemoglobin A.(ABSTRACT TRUNCATED AT 250 WORDS) | ||
==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: oxygen transport]] | [[Category: oxygen transport]] | ||
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Revision as of 17:30, 12 November 2007
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HIGH-RESOLUTION X-RAY STUDY OF DEOXY RECOMBINANT HUMAN HEMOGLOBINS SYNTHESIZED FROM BETA-GLOBINS HAVING MUTATED AMINO TERMINI
OverviewOverview
The crystal structures of three mutant hemoglobins reconstituted from, recombinant beta chains and authentic human alpha chains have been, determined in the deoxy state at 1.8-A resolution. The primary structures, of the mutant hemoglobins differ at the beta-chain amino terminus. One, mutant, beta Met, is characterized by the addition of a methionine at the, amino terminus. The other two hemoglobins are characterized by, substitution of Val 1 beta with either a methionine, beta V1M, or an, alanine, beta V1A. All the mutation-induced structural perturbations are, small intrasubunit changes that are localized to the immediate vicinity of, the beta-chain amino terminus. In the beta Met and beta V1A mutants, the, mobility of the beta-chain amino terminus increases and the electron, density of an associated inorganic anion is decreased. In contrast, the, beta-chain amino terminus of the beta V1M mutant becomes less mobile, and, the inorganic anion binds with increased affinity. These structural, differences can be correlated with functional data for the mutant, hemoglobins [Doyle, M. L., Lew, G., DeYoung, A., Kwiatkowski, L., Noble, R. W., & Ackers, G. K. (1992) Biochemistry preceding paper is this issue], as well as with the properties of ruminant hemoglobins and a mechanism, [Perutz, M., & Imai, K. (1980) J. Mol. Biol. 136, 183-191] that relates, the intrasubunit interactions of the beta-chain amino terminus to changes, in oxygen affinity. Since the structures of the mutant deoxyhemoglobins, show only subtle differences from the structure of deoxyhemoglobin A, it, is concluded that any of the three hemoglobins could probably function as, a surrogate for hemoglobin A.(ABSTRACT TRUNCATED AT 250 WORDS)
DiseaseDisease
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 StructureAbout this Structure
1DXV is a Protein complex structure of sequences from Homo sapiens with SO4 and HEM as ligands. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution X-ray study of deoxy recombinant human hemoglobins synthesized from beta-globins having mutated amino termini., Kavanaugh JS, Rogers PH, Arnone A, Biochemistry. 1992 Sep 15;31(36):8640-7. PMID:1390648
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