5u3i - Revision history

OCA at 13:19, 4 October 2023

OCA — Wed, 04 Oct 2023 13:19:12 GMT

←Older revision		Revision as of 13:19, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5u3i' size='340' side='right'caption='[[5u3i]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='5u3i' size='340' side='right'caption='[[5u3i]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u3i]] is a 4 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=5U3I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5U3I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u3i]] 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=5U3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U3I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7SJ:2-METHOXY-5-({2-[1-(PROPAN-2-YL)-1H-PYRAZOL-5-YL]PYRIDIN-3-YL}METHOXY)PYRIDINE-4-CARBALDEHYDE'>7SJ</scene>, <scene name='pdbligand=CMO:CARBON+MONOXIDE'>CMO</scene>, <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]] 1.95Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ufj\|5ufj]]~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7SJ:2-METHOXY-5-({2-[1-(PROPAN-2-YL)-1H-PYRAZOL-5-YL]PYRIDIN-3-YL}METHOXY)PYRIDINE-4-CARBALDEHYDE'>7SJ</scene>, <scene name='pdbligand=CMO:CARBON+MONOXIDE'>CMO</scene>, <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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5u3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u3i OCA], [~~http~~://pdbe.org/5u3i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5u3i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5u3i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5u3i ProSAT]</span></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=5u3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u3i OCA], [https://pdbe.org/5u3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u3i RCSB], [https://www.ebi.ac.uk/pdbsum/5u3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u3i 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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 30:		Line 30:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Choy~~, R M~~]]	+	[[Category: Choy RM]]
-	[[Category: Li, Z]]	+	[[Category: Li Z]]
-	[[Category: Metcalf, B]]	+	[[Category: Metcalf B]]
-	[[Category: Partridge~~, J R]]~~	+	[[Category: Partridge JR]]
-	~~[[Category: Oxygen transport]]~~	+
-	~~[[Category: R2 quaternary state~~]]	+

OCA at 07:55, 27 November 2019

OCA — Wed, 27 Nov 2019 07:55:13 GMT

←Older revision		Revision as of 07:55, 27 November 2019
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF CARBONMONOXY HEMOGLOBIN S (LIGANDED SICKLE CELL HEMOGLOBIN) COMPLEXED WITH GBT compound 31==		==CRYSTAL STRUCTURE OF CARBONMONOXY HEMOGLOBIN S (LIGANDED SICKLE CELL HEMOGLOBIN) COMPLEXED WITH GBT compound 31==
-	<StructureSection load='5u3i' size='340' side='right' caption='[[5u3i]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='5u3i' size='340' side='right'caption='[[5u3i]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5u3i]] is a 4 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=5U3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U3I FirstGlance]. <br>		<table><tr><td colspan='2'>[[5u3i]] is a 4 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=5U3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U3I FirstGlance]. <br>
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5u3i" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5u3i" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Hemoglobin 3D structures\|Hemoglobin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Choy, R M]]		[[Category: Choy, R M]]
	[[Category: Li, Z]]		[[Category: Li, Z]]

OCA at 04:57, 12 April 2017

OCA — Wed, 12 Apr 2017 04:57:49 GMT

←Older revision		Revision as of 04:57, 12 April 2017
Line 12:		Line 12:
	== 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>		[[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We report the discovery of a new potent allosteric effector of sickle cell hemoglobin, GBT440 (36), that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, 36 binds with a 1:1 stoichiometry. Compound 36 is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of approximately 150. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations. GBT440 (36) is in Phase 3 clinical trials for the treatment of sickle cell disease (NCT03036813).
		+
		+	Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin.,Metcalf B, Chuang C, Dufu K, Patel MP, Silva-Garcia A, Johnson C, Lu Q, Partridge JR, Patskovska L, Patskovsky Y, Almo SC, Jacobson MP, Hua L, Xu Q, Gwaltney SL 2nd, Yee C, Harris J, Morgan BP, James J, Xu D, Hutchaleelaha A, Paulvannan K, Oksenberg D, Li Z ACS Med Chem Lett. 2017 Jan 23;8(3):321-326. doi: 10.1021/acsmedchemlett.6b00491., eCollection 2017 Mar 9. PMID:28337324<ref>PMID:28337324</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5u3i" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 01:43, 11 March 2017

OCA — Sat, 11 Mar 2017 01:43:21 GMT

←Older revision		Revision as of 01:43, 11 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5u3i is ~~ON HOLD~~	+	==CRYSTAL STRUCTURE OF CARBONMONOXY HEMOGLOBIN S (LIGANDED SICKLE CELL HEMOGLOBIN) COMPLEXED WITH GBT compound 31==
-		+	<StructureSection load='5u3i' size='340' side='right' caption='[[5u3i]], [[Resolution\|resolution]] 1.95Å' scene=''>
-	~~Authors~~: ~~Partridge~~, J.R., ~~Choy~~, R.M., Li, Z., ~~Metcalf~~, B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5u3i]] is a 4 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=5U3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U3I FirstGlance]. <br>
-	~~Description~~: ~~CRYSTAL STRUCTURE OF CARBONMONOXY HEMOGLOBIN~~ S (~~LIGANDED SICKLE CELL HEMOGLOBIN~~) ~~COMPLEXED WITH GBT compound 31~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7SJ:2-METHOXY-5-({2-[1-(PROPAN-2-YL)-1H-PYRAZOL-5-YL]PYRIDIN-3-YL}METHOXY)PYRIDINE-4-CARBALDEHYDE'>7SJ</scene>, <scene name='pdbligand=CMO:CARBON+MONOXIDE'>CMO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ufj\|5ufj]]</td></tr>
-	[[~~Category~~: ~~Partridge~~, J.R]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u3i OCA], [http://pdbe.org/5u3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u3i RCSB], [http://www.ebi.ac.uk/pdbsum/5u3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u3i ProSAT]</span></td></tr>
-	[[Category: Choy, R.M]]	+	</table>
		+	== 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>
		+	== 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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Choy, R M]]
		+	[[Category: Li, Z]]
	[[Category: Metcalf, B]]		[[Category: Metcalf, B]]
-	[[Category: Li, Z]]	+	[[Category: Partridge, J R]]
		+	[[Category: Oxygen transport]]
		+	[[Category: R2 quaternary state]]

OCA: Protected "5u3i" [edit=sysop:move=sysop]

OCA — Thu, 15 Dec 2016 17:37:18 GMT

Protected "5u3i" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:37, 15 December 2016

OCA: New page: '''Unreleased structure''' The entry 5u3i is ON HOLD Authors: Partridge, J.R., Choy, R.M., Li, Z., Metcalf, B. Description: CRYSTAL STRUCTURE OF CARBONMONOXY HEMOGLOBIN S (LIGANDED SIC...

OCA — Thu, 15 Dec 2016 17:37:17 GMT

New page: '''Unreleased structure''' The entry 5u3i is ON HOLD Authors: Partridge, J.R., Choy, R.M., Li, Z., Metcalf, B. Description: CRYSTAL STRUCTURE OF CARBONMONOXY HEMOGLOBIN S (LIGANDED SIC...

New page

'''Unreleased structure'''

The entry 5u3i is ON HOLD

Authors: Partridge, J.R., Choy, R.M., Li, Z., Metcalf, B.

Description: CRYSTAL STRUCTURE OF CARBONMONOXY HEMOGLOBIN S (LIGANDED SICKLE CELL HEMOGLOBIN) COMPLEXED WITH GBT compound 31
[[Category: Unreleased Structures]]
[[Category: Partridge, J.R]]
[[Category: Choy, R.M]]
[[Category: Metcalf, B]]
[[Category: Li, Z]]