1c7d
From Proteopedia
DEOXY RHB1.2 (RECOMBINANT HEMOGLOBIN)
Structural highlights
Disease[HBB_HUMAN] Defects in HBB 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.[1] [2] [3] [4] Defects in HBB are the cause of beta-thalassemia (B-THAL) [MIM:613985]. A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of beta-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. Absence of beta chain causes beta(0)-thalassemia, while reduced amounts of detectable beta globin causes beta(+)-thalassemia. In the severe forms of beta-thalassemia, the excess alpha globin chains accumulate in the developing erythroid precursors in the marrow. Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe microcytic hypochromic anemia. Clinically, beta-thalassemia is divided into thalassemia major which is transfusion dependent, thalassemia intermedia (of intermediate severity), and thalassemia minor that is asymptomatic.[5] Defects in HBB are the cause of sickle cell anemia (SKCA) [MIM:603903]; also known as sickle cell disease. Sickle cell anemia is characterized by abnormally shaped red cells resulting in chronic anemia and periodic episodes of pain, serious infections and damage to vital organs. Normal red blood cells are round and flexible and flow easily through blood vessels, but in sickle cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They are C-shaped and resembles a sickle. These stiffer red blood cells can led to microvascular occlusion thus cutting off the blood supply to nearby tissues. Defects in HBB are the cause of beta-thalassemia dominant inclusion body type (B-THALIB) [MIM:603902]. An autosomal dominant form of beta thalassemia characterized by moderate anemia, lifelong jaundice, cholelithiasis and splenomegaly, marked morphologic changes in the red cells, erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large inclusion bodies in the normoblasts, both in the marrow and in the peripheral blood after splenectomy.[6] Function[HBB_HUMAN] Involved in oxygen transport from the lung to the various peripheral tissues.[7] LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.[8] 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 PubMedThe crystal structures of three recombinant human hemoglobins, rHb1. 0, rHb1.1 and rHb1.2, have been determined in the deoxy state at 1.8 A resolution. Two of the three proteins, rHb1.1 and rHb1.2, contain a genetic fusion of the alpha subunits, a one- or two-glycine link, respectively, whereas rHb1.0 does not. The glycine crosslinks, localized between one N- and C--termini pair of the alpha subunits in the deoxy crystalline state, do not perturb the overall tertiary or quaternary or even the local structure of hemoglobin. Therefore, genetic fusion to prevent the dissociation of the hemoglobin tetramer, thereby inhibiting renal clearance based upon molecular size, is a structurally conservative method to stabilize hemoglobin for use as an oxygen-delivery therapeutic. Genetically crosslinked hemoglobin: a structural study.,Brucker EA Acta Crystallogr D Biol Crystallogr. 2000 Jul;56(Pt 7):812-6. PMID:10930828[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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