1sdl: Difference between revisions
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==Overview== | ==Overview== | ||
The structural end-points of haemoglobin's transition from its, low-oxygen-affinity (T) to high-oxygen-affinity (R) state, have been well, established by X-ray crystallography, but short-lived intermediates have, proved less amenable to X-ray studies. Here we use chemical crosslinking, to fix these intermediates for structural characterization. We describe, the X-ray structures of three haemoglobins, alpha 2 beta 1S82 beta, alpha, 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, which were crosslinked, between the amino groups of residues beta Val1 and beta Lys82 by, 3,3'-stilbenedicarboxylic acid (S) or trimesic acid (Tm) while in the, deoxy state, and saturated with carbon monoxide before crystallization., alpha 2 beta 1S82 beta, which has almost normal oxygen affinity, is, completely in the R-state conformation; however, alpha 2 beta 1Tm82 beta, and alpha 2 beta 1,82Tm82 beta, both of which have low oxygen affinity, have been prevented from completing their transition into the R state and, display many features of a transitional intermediate. These haemoglobins, therefore represent a snapshot of the nascent R state. | The structural end-points of haemoglobin's transition from its, low-oxygen-affinity (T) to high-oxygen-affinity (R) state, have been well, established by X-ray crystallography, but short-lived intermediates have, proved less amenable to X-ray studies. Here we use chemical crosslinking, to fix these intermediates for structural characterization. We describe, the X-ray structures of three haemoglobins, alpha 2 beta 1S82 beta, alpha, 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, which were crosslinked, between the amino groups of residues beta Val1 and beta Lys82 by, 3,3'-stilbenedicarboxylic acid (S) or trimesic acid (Tm) while in the, deoxy state, and saturated with carbon monoxide before crystallization., alpha 2 beta 1S82 beta, which has almost normal oxygen affinity, is, completely in the R-state conformation; however, alpha 2 beta 1Tm82 beta, and alpha 2 beta 1,82Tm82 beta, both of which have low oxygen affinity, have been prevented from completing their transition into the R state and, display many features of a transitional intermediate. These haemoglobins, therefore represent a snapshot of the nascent R state. | ||
==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: respiratory protein]] | [[Category: respiratory protein]] | ||
''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 19:12:49 2007'' | ||
Revision as of 20:06, 12 November 2007
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CROSS-LINKED, CARBONMONOXY HEMOGLOBIN A
OverviewOverview
The structural end-points of haemoglobin's transition from its, low-oxygen-affinity (T) to high-oxygen-affinity (R) state, have been well, established by X-ray crystallography, but short-lived intermediates have, proved less amenable to X-ray studies. Here we use chemical crosslinking, to fix these intermediates for structural characterization. We describe, the X-ray structures of three haemoglobins, alpha 2 beta 1S82 beta, alpha, 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, which were crosslinked, between the amino groups of residues beta Val1 and beta Lys82 by, 3,3'-stilbenedicarboxylic acid (S) or trimesic acid (Tm) while in the, deoxy state, and saturated with carbon monoxide before crystallization., alpha 2 beta 1S82 beta, which has almost normal oxygen affinity, is, completely in the R-state conformation; however, alpha 2 beta 1Tm82 beta, and alpha 2 beta 1,82Tm82 beta, both of which have low oxygen affinity, have been prevented from completing their transition into the R state and, display many features of a transitional intermediate. These haemoglobins, therefore represent a snapshot of the nascent R state.
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
1SDL is a Protein complex structure of sequences from Homo sapiens with HEM, CMO and TMM as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Allosteric transition intermediates modelled by crosslinked haemoglobins., Schumacher MA, Dixon MM, Kluger R, Jones RT, Brennan RG, Nature. 1995 May 4;375(6526):84-7. PMID:7723849
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