1y01

<StructureSection load='1y01' size='340' side='right' caption='[[1y01]], [[Resolution|resolution]] 2.80&Aring;' scene=''>

<table><tr><td colspan='2'>[[1y01]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y01 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y01 FirstGlance]. <br>

</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHK:6-[(CYCLOHEXYLACETYL)(2-HYDROXYETHYL)AMINO]-6-DEOXY-D-XYLO-HEXITOL'>CHK</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene><br>

<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AHSP, EDRF, ERAF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), HBA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>

<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1y01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y01 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1y01 RCSB], [http://www.ebi.ac.uk/pdbsum/1y01 PDBsum]</span></td></tr>

[[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/AHSP_HUMAN AHSP_HUMAN]] Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation. It is predicted to modulate pathological states of alpha-hemoglobin excess such as beta-thalassemia.<ref>PMID:12066189</ref> [[http://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN]] Involved in oxygen transport from the lung to the various peripheral tissues.

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/y0/1y01_consurf.spt"</scriptWhenChecked>

</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/chain_selection.php?pdb_ID=2ata ConSurf].

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin.,Feng L, Gell DA, Zhou S, Gu L, Kong Y, Li J, Hu M, Yan N, Lee C, Rich AM, Armstrong RS, Lay PA, Gow AJ, Weiss MJ, Mackay JP, Shi Y Cell. 2004 Nov 24;119(5):629-40. PMID:15550245<ref>PMID:15550245</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

[[Category: Feng, L.]]

[[Category: Gell, D A.]]

[[Category: Gow, A J.]]

[[Category: Gu, L.]]

[[Category: Mackay, J P.]]

[[Category: Shi, Y.]]

[[Category: Weiss, M J.]]

[[Category: Zhou, S.]]

[[Category: Stabilization of alpha hemoglobin]]