4hhb

THE CRYSTAL STRUCTURE OF HUMAN DEOXYHAEMOGLOBIN AT 1.74 ANGSTROMS RESOLUTION

spinqualitylabelsall models 4hhb, resolution 1.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hhb is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.74Å Ligands: HEM, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease HBA_HUMAN Defects in HBA1 may be a cause of Heinz body anemias (HEIBAN) [MIM:140700. This is a form of non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency. Defects in HBA1 are the cause of alpha-thalassemia (A-THAL) [MIM:604131. The thalassemias are the most common monogenic diseases and occur mostly in Mediterranean and Southeast Asian populations. The hallmark of alpha-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. The level of alpha chain production can range from none to very nearly normal levels. Deletion of both copies of each of the two alpha-globin genes causes alpha(0)-thalassemia, also known as homozygous alpha thalassemia. Due to the complete absence of alpha chains, the predominant fetal hemoglobin is a tetramer of gamma-chains (Bart hemoglobin) that has essentially no oxygen carrying capacity. This causes oxygen starvation in the fetal tissues leading to prenatal lethality or early neonatal death. The loss of three alpha genes results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia known as hemoglobin H disease. Untreated, most patients die in childhood or early adolescence. The loss of two alpha genes results in mild alpha-thalassemia, also known as heterozygous alpha-thalassemia. Affected individuals have small red cells and a mild anemia (microcytosis). If three of the four alpha-globin genes are functional, individuals are completely asymptomatic. Some rare forms of alpha-thalassemia are due to point mutations (non-deletional alpha-thalassemia). The thalassemic phenotype is due to unstable globin alpha chains that are rapidly catabolized prior to formation of the alpha-beta heterotetramers. Note=Alpha(0)-thalassemia is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders. Defects in HBA1 are the cause of hemoglobin H disease (HBH) [MIM:613978. HBH is a form of alpha-thalassemia due to the loss of three alpha genes. This results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia. Untreated, most patients die in childhood or early adolescence. Function HBA_HUMAN Involved in oxygen transport from the lung to the various peripheral tissues. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The structure of human deoxyhaemoglobin was refined at 1.74 A resolution using data collected on film at room temperature from a synchrotron X-ray source. The crystallographic R-factor is 16.0%. The estimated error in atomic positions is 0.1 A overall, 0.14 A for main-chain atoms of internal segments, and 0.05 A for the iron atoms. The effects of intermolecular contacts on the structure were investigated; such contacts cause only highly localized distortions, as judged from the degree of molecular asymmetry that they induce. The geometry of the iron-nitrogen complex closely resembles that of the deoxymyoglobin structure of Takano (1977) and of the 5-co-ordinated model compounds of Hoard (1975) and Jameson et al. (1980). The distance of the iron from the mean plane of N(porphyrin) is 0.40(5) A and 0.36(5) A, respectively, at the alpha and beta haems, in contrast to the corresponding distance of +0.12(8) A and -0.11(8) A in oxyhaemoglobin ( Shaanan , 1983); the Fe-N epsilon (F8) bond length is 2.12(4) A and the Fe-N(porphyrin) bond length is 2.06(2) A; the last is also in good agreement with extended X-ray fluorescence spectroscopy measurements on deoxyhaemoglobin ( Eisenberger et al., 1978; Perutz et al., 1982). The haems are domed toward the proximal side; the separation between the mean planes of N(porphyrin) and C(porphyrin) being 0.16(6) A and 0.10(6) A, respectively at the alpha and beta haems. At the alpha haems, the normals to the mean pyrrole planes are tilted uniformly toward the haem centre, by about three degrees relative to the haem normal, and there is a folding of about four degrees of the haem about an axis running between the methene carbons that are between the pyrrole rings bearing like-type side-chains. At the beta haems, there is no such folding, and only pyrroles II and IV (those eclipsed by His F8) are appreciably tilted, by about eight degrees. The independence of these parameters from restraints imposed on the model was verified by unrestrained refinement of the entire molecule starting from a structure with modified haem geometry. The crystal structure of human deoxyhaemoglobin at 1.74 A resolution.,Fermi G, Perutz MF, Shaanan B, Fourme R J Mol Biol. 1984 May 15;175(2):159-74. PMID:6726807 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hemoglobin 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA