1gli: Difference between revisions
New page: left|200px<br /> <applet load="1gli" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gli, resolution 2.5Å" /> '''DEOXYHEMOGLOBIN T38W... |
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==Overview== | ==Overview== | ||
The allosteric transition of hemoglobin involves an extensive, reorganization of the alpha 1 beta 2 interface, in which two contact, regions have been identified. This paper concerns at the effect of two, mutations located in the "switch" (alpha C3 Thr --> Trp) and the "flexible, joint" (beta C3 Trp --> Thr). We have expressed and characterized one, double and two single mutants: Hb alpha T38W/beta W37T, Hb beta W37T, and, Hb alpha T38W, whose structure has been determined by crystallography. We, present data on: (i) the interface structure in the contact regions, (ii), oxygen and CO binding kinetics and cooperativity, (iii) dissociation rates, of deoxy tetramers and association rates of deoxy dimers, and (iv) the, effect of NaI on deoxy tetramer dissociation rate constant. All the, mutants are tetrameric and T-state in the deoxygenated derivative., Reassociation of deoxygenated dimers is not modified by interface, mutations. DeoxyHb alpha T38W/beta W37T dissociate much faster. We propose, a binding site for I- at the switch region. The single mutants binds O2, cooperatively; the double one is almost non-cooperative, a feature, confirmed by CO binding. The functional data, analyzed with the two-state, model, indicate that these mutations reduce the value of the allosteric, constant LO. | The allosteric transition of hemoglobin involves an extensive, reorganization of the alpha 1 beta 2 interface, in which two contact, regions have been identified. This paper concerns at the effect of two, mutations located in the "switch" (alpha C3 Thr --> Trp) and the "flexible, joint" (beta C3 Trp --> Thr). We have expressed and characterized one, double and two single mutants: Hb alpha T38W/beta W37T, Hb beta W37T, and, Hb alpha T38W, whose structure has been determined by crystallography. We, present data on: (i) the interface structure in the contact regions, (ii), oxygen and CO binding kinetics and cooperativity, (iii) dissociation rates, of deoxy tetramers and association rates of deoxy dimers, and (iv) the, effect of NaI on deoxy tetramer dissociation rate constant. All the, mutants are tetrameric and T-state in the deoxygenated derivative., Reassociation of deoxygenated dimers is not modified by interface, mutations. DeoxyHb alpha T38W/beta W37T dissociate much faster. We propose, a binding site for I- at the switch region. The single mutants binds O2, cooperatively; the double one is almost non-cooperative, a feature, confirmed by CO binding. The functional data, analyzed with the two-state, model, indicate that these mutations reduce the value of the allosteric, constant LO. | ||
==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: site directed mutant]] | [[Category: site directed mutant]] | ||
''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 17:06:51 2007'' | ||
Revision as of 18:00, 12 November 2007
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DEOXYHEMOGLOBIN T38W (ALPHA CHAINS), V1G (ALPHA AND BETA CHAINS)
OverviewOverview
The allosteric transition of hemoglobin involves an extensive, reorganization of the alpha 1 beta 2 interface, in which two contact, regions have been identified. This paper concerns at the effect of two, mutations located in the "switch" (alpha C3 Thr --> Trp) and the "flexible, joint" (beta C3 Trp --> Thr). We have expressed and characterized one, double and two single mutants: Hb alpha T38W/beta W37T, Hb beta W37T, and, Hb alpha T38W, whose structure has been determined by crystallography. We, present data on: (i) the interface structure in the contact regions, (ii), oxygen and CO binding kinetics and cooperativity, (iii) dissociation rates, of deoxy tetramers and association rates of deoxy dimers, and (iv) the, effect of NaI on deoxy tetramer dissociation rate constant. All the, mutants are tetrameric and T-state in the deoxygenated derivative., Reassociation of deoxygenated dimers is not modified by interface, mutations. DeoxyHb alpha T38W/beta W37T dissociate much faster. We propose, a binding site for I- at the switch region. The single mutants binds O2, cooperatively; the double one is almost non-cooperative, a feature, confirmed by CO binding. The functional data, analyzed with the two-state, model, indicate that these mutations reduce the value of the allosteric, constant LO.
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
1GLI is a Protein complex structure of sequences from Homo sapiens with PO4 and HEM as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Probing the alpha 1 beta 2 interface of human hemoglobin by mutagenesis. Role of the FG-C contact regions., Vallone B, Bellelli A, Miele AE, Brunori M, Fermi G, J Biol Chem. 1996 May 24;271(21):12472-80. PMID:8647854
Page seeded by OCA on Mon Nov 12 17:06:51 2007