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| ==Structure of Hemoglobin Complex with 18-crown-6== | | ==Structure of Hemoglobin Complex with 18-crown-6== |
| <StructureSection load='3whm' size='340' side='right'caption='[[3whm]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='3whm' size='340' side='right'caption='[[3whm]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3whm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHM FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHM FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=O4B:1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE'>O4B</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene></td></tr> | | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3whm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whm OCA], [https://pdbe.org/3whm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whm RCSB], [https://www.ebi.ac.uk/pdbsum/3whm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whm ProSAT]</span></td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wh0|3wh0]]</div></td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3whm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whm OCA], [https://pdbe.org/3whm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whm RCSB], [https://www.ebi.ac.uk/pdbsum/3whm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whm ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Disease ==
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| [[https://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN]] Defects in HBA1 may be a cause of Heinz body anemias (HEIBAN) [MIM:[https://omim.org/entry/140700 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.<ref>PMID:2833478</ref> Defects in HBA1 are the cause of alpha-thalassemia (A-THAL) [MIM:[https://omim.org/entry/604131 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:[https://omim.org/entry/613978 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.<ref>PMID:10569720</ref> [[https://www.uniprot.org/uniprot/HBB_HUMAN HBB_HUMAN]] Defects in HBB may be a cause of Heinz body anemias (HEIBAN) [MIM:[https://omim.org/entry/140700 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.<ref>PMID:186485</ref> <ref>PMID:6259091</ref> <ref>PMID:2599881</ref> <ref>PMID:8704193</ref> Defects in HBB are the cause of beta-thalassemia (B-THAL) [MIM:[https://omim.org/entry/613985 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.<ref>PMID:1971109</ref> Defects in HBB are the cause of sickle cell anemia (SKCA) [MIM:[https://omim.org/entry/603903 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:[https://omim.org/entry/603902 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.<ref>PMID:1971109</ref>
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| == Function ==
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| [[https://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN]] Involved in oxygen transport from the lung to the various peripheral tissues. [[https://www.uniprot.org/uniprot/HBB_HUMAN HBB_HUMAN]] Involved in oxygen transport from the lung to the various peripheral tissues.<ref>PMID:16904236</ref> LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.<ref>PMID:16904236</ref>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Crown ethers are small, cyclic polyethers that have found wide-spread use in phase-transfer catalysis and, to a certain degree, in protein chemistry. Crown ethers readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6. We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols. Our studies show that crown ethers can modify protein surface behavior dramatically by stabilizing either intra- or intermolecular interactions. Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain-domain interactions, stabilization in organic solvents, and crystallization.
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| Crowning Proteins: Modulating the Protein Surface Properties using Crown Ethers.,Lee CC, Maestre-Reyna M, Hsu KC, Wang HC, Liu CI, Jeng WY, Lin LL, Wood R, Chou CC, Yang JM, Wang AH Angew Chem Int Ed Engl. 2014 Oct 6. doi: 10.1002/anie.201405664. PMID:25287606<ref>PMID:25287606</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3whm" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Hemoglobin 3D structures|Hemoglobin 3D structures]] | | *[[Hemoglobin 3D structures|Hemoglobin 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Lee, C C]] | | [[Category: Lee CC]] |
| [[Category: Lin, L L]] | | [[Category: Lin LL]] |
| [[Category: Wang, A H.J]] | | [[Category: Wang AHJ]] |
| [[Category: 18-crown-6]]
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| [[Category: Heme-binding protein]]
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