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<StructureSection load='2hbs' size='340' side='right'caption='[[2hbs]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
<StructureSection load='2hbs' size='340' side='right'caption='[[2hbs]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2hbs]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The May 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Hemoglobin''  by Shuchismita Dutta and David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_5 10.2210/rcsb_pdb/mom_2003_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HBS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2HBS FirstGlance]. <br>
<table><tr><td colspan='2'>[[2hbs]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The May 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Hemoglobin''  by Shuchismita Dutta and David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_5 10.2210/rcsb_pdb/mom_2003_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HBS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HBS 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></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2hbs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hbs OCA], [http://pdbe.org/2hbs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hbs RCSB], [http://www.ebi.ac.uk/pdbsum/2hbs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hbs ProSAT]</span></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></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=2hbs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hbs OCA], [https://pdbe.org/2hbs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hbs RCSB], [https://www.ebi.ac.uk/pdbsum/2hbs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hbs ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN]] Defects in HBA1 may be a cause of Heinz body anemias (HEIBAN) [MIM:[http://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:[http://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:[http://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> [[http://www.uniprot.org/uniprot/HBB_HUMAN HBB_HUMAN]] Defects in HBB may be a cause of Heinz body anemias (HEIBAN) [MIM:[http://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:[http://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:[http://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:[http://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> 
[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>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN]] Involved in oxygen transport from the lung to the various peripheral tissues. [[http://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> 
[https://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN] Involved in oxygen transport from the lung to the various peripheral tissues.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hbs ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hbs ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have refined the crystal structure of deoxyhemoglobin S (beta Glu6--&gt;Val) at 2.05 A resolution to an R-factor of 16.5% (free R=21. 5%) using crystals isomorphous to those originally grown by Wishner and Love. A predominant feature of this crystal form is a double strand of hemoglobin tetramers that has been shown by a variety of techniques to be the fundamental building block of the intracellular sickle cell fiber. The double strand is stabilized by lateral contacts involving the mutant valine interacting with a pocket between the E and F helices on another tetramer. The new structure reveals some marked differences from the previously refined 3.0 A resolution structure, including several residues in the lateral contact which have shifted by as much as 3.5 A. The lateral contact includes, in addition to the hydrophobic interactions involving the mutant valine, hydrophilic interactions and bridging water molecules at the periphery of the contact. This structure provides further insights into hemoglobin polymerization and may be useful for the structure-based design of therapeutic agents to treat sickle cell disease.
The high resolution crystal structure of deoxyhemoglobin S.,Harrington DJ, Adachi K, Royer WE Jr J Mol Biol. 1997 Sep 26;272(3):398-407. PMID:9325099<ref>PMID:9325099</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2hbs" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Ann Taylor/Hemoglobin|Ann Taylor/Hemoglobin]]
*[[Hemoglobin|Hemoglobin]]
*[[Hemoglobin|Hemoglobin]]
*[[Hemoglobin 3D structures|Hemoglobin 3D structures]]
*[[Hemoglobin 3D structures|Hemoglobin 3D structures]]
*[[Sandbox 12345|Sandbox 12345]]
*[[Sandbox 12345|Sandbox 12345]]
*[[User:Murtaza Anssar|User:Murtaza Anssar]]
== References ==
== References ==
<references/>
<references/>
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[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Adachi, K]]
[[Category: Adachi K]]
[[Category: Harrington, D J]]
[[Category: Harrington DJ]]
[[Category: Junior, W E.Royer]]
[[Category: Royer Junior WE]]
[[Category: Oxygen transport]]

Latest revision as of 12:31, 14 February 2024

THE HIGH RESOLUTION CRYSTAL STRUCTURE OF DEOXYHEMOGLOBIN STHE HIGH RESOLUTION CRYSTAL STRUCTURE OF DEOXYHEMOGLOBIN S

Structural highlights

2hbs is a 8 chain structure with sequence from Homo sapiens. The May 2003 RCSB PDB Molecule of the Month feature on Hemoglobin by Shuchismita Dutta and David S. Goodsell is 10.2210/rcsb_pdb/mom_2003_5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.05Å
Ligands:
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.[1] 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.[2]

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.

See Also

References

  1. ↑ Ohba Y, Yamamoto K, Hattori Y, Kawata R, Miyaji T. Hyperunstable hemoglobin Toyama [alpha 2 136(H19)Leu----Arg beta 2]: detection and identification by in vitro biosynthesis with radioactive amino acids. Hemoglobin. 1987;11(6):539-56. PMID:2833478
  2. ↑ Traeger-Synodinos J, Harteveld CL, Kanavakis E, Giordano PC, Kattamis C, Bernini LF. Hb Aghia Sophia [alpha62(E11)Val-->0 (alpha1)], an "in-frame" deletion causing alpha-thalassemia. Hemoglobin. 1999 Nov;23(4):317-24. PMID:10569720

2hbs, resolution 2.05Å

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