5x2s - Revision history

OCA at 10:17, 27 March 2024

2024-03-27T10:17:00Z

←Older revision		Revision as of 10:17, 27 March 2024
Line 3:		Line 3:
	<StructureSection load='5x2s' size='340' side='right'caption='[[5x2s]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='5x2s' size='340' side='right'caption='[[5x2s]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5x2s]] is a 12 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=5X2S OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5X2S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5x2s]] is a 12 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=5X2S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X2S 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=HNI:PROTOPORPHYRIN+IX+CONTAINING+NI(II)'>HNI</scene>, <scene name='pdbligand=PEM:2-[P-[2-P-CHLOROBENZAMIDO)ETHYL]PHENOXY]-2-METHYLPROPIONIC+ACID'>PEM</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]] 2.39Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5x2r\|5x2r]], [[5x2t\|5x2t]], [[5x2u\|5x2u]]~~</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=HNI:PROTOPORPHYRIN+IX+CONTAINING+NI(II)'>HNI</scene>, <scene name='pdbligand=PEM:2-[P-[2-P-CHLOROBENZAMIDO)ETHYL]PHENOXY]-2-METHYLPROPIONIC+ACID'>PEM</scene></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=5x2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x2s OCA], [~~http~~://pdbe.org/5x2s PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5x2s RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5x2s PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5x2s 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=5x2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x2s OCA], [https://pdbe.org/5x2s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x2s RCSB], [https://www.ebi.ac.uk/pdbsum/5x2s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x2s 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Although X-ray crystallography is the most commonly used technique for studying the molecular structure of proteins, it is not generally able to monitor the dynamic changes or global domain motions that often underlie allostery. These motions often prevent crystal growth or reduce crystal order. We have recently discovered a crystal form of human hemoglobin that contains three protein molecules allowed to express a full range of quaternary structures, whereas maintaining strong X-ray diffraction. Here we use this crystal form to investigate the effects of two allosteric effectors, phosphate and bezafibrate, by tracking the structures and functions of the three hemoglobin molecules following the addition of each effector. The X-ray analysis shows that the addition of either phosphate or bezafibrate not only induces conformational changes in a direction from a relaxed-state to a tense-state, but also within relaxed-state populations. The microspectrophotometric O2 equilibrium measurements on the crystals demonstrate that the binding of each effector energetically stabilizes the lowest affinity conformer more strongly than the intermediate affinity one, thereby reducing the O2 affinity of tense-state populations, and that the addition of bezafibrate causes an approximately 5-fold decrease in the O2 affinity of relaxed-state populations. These results show that the allosteric pathway of hemoglobin involves shifts of populations rather than a unidirectional conversion of one quaternary structure to another, and that minor conformers of hemoglobin may have a disproportionate effect on the overall O2 affinity.	+
-		+
-	Direct observation of conformational population shifts in crystalline human hemoglobin.,Shibayama N, Ohki M, Tame JRH, Park SY J Biol Chem. 2017 Nov 3;292(44):18258-18269. doi: 10.1074/jbc.M117.781146. Epub, 2017 Sep 20. PMID:28931607<ref>PMID:28931607</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5x2s" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 30:		Line 21:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ohki, M]]	+	[[Category: Ohki M]]
-	[[Category: Park, S Y]]	+	[[Category: Park S-Y]]
-	~~[[Category: Allosteric protein]]~~	+
-	~~[[Category: Allostery]]~~	+
-	~~[[Category: Bezafibrate]]~~	+
-	~~[[Category: Hemoglobin]]~~	+
-	~~[[Category: Oxygen binding]]~~	+
-	~~[[Category: Transport protein~~]]	+

OCA at 07:23, 7 October 2020

2020-10-07T07:23:19Z

←Older revision		Revision as of 07:23, 7 October 2020
Line 1:		Line 1:

	==Direct Observation of Conformational Population Shifts in Hemoglobin: Crystal Structure of Half-Liganded Hemoglobin after Adding 4 mM bezafibrate pH 6.5.==		==Direct Observation of Conformational Population Shifts in Hemoglobin: Crystal Structure of Half-Liganded Hemoglobin after Adding 4 mM bezafibrate pH 6.5.==
-	<StructureSection load='5x2s' size='340' side='right' caption='[[5x2s]], [[Resolution\|resolution]] 2.39Å' scene=''>	+	<StructureSection load='5x2s' size='340' side='right'caption='[[5x2s]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5x2s]] is a 12 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=5X2S OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5X2S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5x2s]] is a 12 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=5X2S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5X2S FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HNI:PROTOPORPHYRIN+IX+CONTAINING+NI(II)'>HNI</scene>, <scene name='pdbligand=PEM:2-[P-[2-P-CHLOROBENZAMIDO)ETHYL]PHENOXY]-2-METHYLPROPIONIC+ACID'>PEM</scene></td></tr>	+	</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=HNI:PROTOPORPHYRIN+IX+CONTAINING+NI(II)'>HNI</scene>, <scene name='pdbligand=PEM:2-[P-[2-P-CHLOROBENZAMIDO)ETHYL]PHENOXY]-2-METHYLPROPIONIC+ACID'>PEM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5x2r\|5x2r]], [[5x2t\|5x2t]], [[5x2u\|5x2u]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5x2r\|5x2r]], [[5x2t\|5x2t]], [[5x2u\|5x2u]]</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=5x2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x2s OCA], [http://pdbe.org/5x2s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x2s RCSB], [http://www.ebi.ac.uk/pdbsum/5x2s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x2s ProSAT]</span></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=5x2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x2s OCA], [http://pdbe.org/5x2s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x2s RCSB], [http://www.ebi.ac.uk/pdbsum/5x2s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x2s ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5x2s" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5x2s" 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: Ohki, M]]		[[Category: Ohki, M]]
	[[Category: Park, S Y]]		[[Category: Park, S Y]]

OCA at 06:44, 20 December 2017

2017-12-20T06:44:38Z

←Older revision		Revision as of 06:44, 20 December 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 ==
		+	Although X-ray crystallography is the most commonly used technique for studying the molecular structure of proteins, it is not generally able to monitor the dynamic changes or global domain motions that often underlie allostery. These motions often prevent crystal growth or reduce crystal order. We have recently discovered a crystal form of human hemoglobin that contains three protein molecules allowed to express a full range of quaternary structures, whereas maintaining strong X-ray diffraction. Here we use this crystal form to investigate the effects of two allosteric effectors, phosphate and bezafibrate, by tracking the structures and functions of the three hemoglobin molecules following the addition of each effector. The X-ray analysis shows that the addition of either phosphate or bezafibrate not only induces conformational changes in a direction from a relaxed-state to a tense-state, but also within relaxed-state populations. The microspectrophotometric O2 equilibrium measurements on the crystals demonstrate that the binding of each effector energetically stabilizes the lowest affinity conformer more strongly than the intermediate affinity one, thereby reducing the O2 affinity of tense-state populations, and that the addition of bezafibrate causes an approximately 5-fold decrease in the O2 affinity of relaxed-state populations. These results show that the allosteric pathway of hemoglobin involves shifts of populations rather than a unidirectional conversion of one quaternary structure to another, and that minor conformers of hemoglobin may have a disproportionate effect on the overall O2 affinity.
		+
		+	Direct observation of conformational population shifts in crystalline human hemoglobin.,Shibayama N, Ohki M, Tame JRH, Park SY J Biol Chem. 2017 Nov 3;292(44):18258-18269. doi: 10.1074/jbc.M117.781146. Epub, 2017 Sep 20. PMID:28931607<ref>PMID:28931607</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5x2s" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:49, 6 November 2017

2017-11-06T11:49:12Z

←Older revision		Revision as of 11:49, 6 November 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5x2s is ON HOLD~~	+	==Direct Observation of Conformational Population Shifts in Hemoglobin: Crystal Structure of Half-Liganded Hemoglobin after Adding 4 mM bezafibrate pH 6.5.==
-		+	<StructureSection load='5x2s' size='340' side='right' caption='[[5x2s]], [[Resolution\|resolution]] 2.39Å' scene=''>
-	~~Authors: Ohki, M., Park, S.-Y.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5x2s]] is a 12 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=5X2S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X2S FirstGlance]. <br>
-	~~Description:~~ Direct Observation of Conformational Population Shifts in Hemoglobin: Crystal Structure of Half-Liganded Hemoglobin after Adding 4 mM bezafibrate pH 6.5.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HNI:PROTOPORPHYRIN+IX+CONTAINING+NI(II)'>HNI</scene>, <scene name='pdbligand=PEM:2-[P-[2-P-CHLOROBENZAMIDO)ETHYL]PHENOXY]-2-METHYLPROPIONIC+ACID'>PEM</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5x2r\|5x2r]], [[5x2t\|5x2t]], [[5x2u\|5x2u]]</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=5x2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x2s OCA], [http://pdbe.org/5x2s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x2s RCSB], [http://www.ebi.ac.uk/pdbsum/5x2s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x2s ProSAT]</span></td></tr>
		+	</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: Ohki, M]]		[[Category: Ohki, M]]
-	[[Category: Park, S.-Y]]	+	[[Category: Park, S Y]]
		+	[[Category: Allosteric protein]]
		+	[[Category: Allostery]]
		+	[[Category: Bezafibrate]]
		+	[[Category: Hemoglobin]]
		+	[[Category: Oxygen binding]]
		+	[[Category: Transport protein]]

OCA: Protected "5x2s" [edit=sysop:move=sysop]

2017-03-09T15:40:39Z

Protected "5x2s" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:40, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5x2s is ON HOLD Authors: Ohki, M., Park, S.-Y. Description: Direct Observation of Conformational Population Shifts in Hemoglobin: Crystal Structure...

2017-03-09T15:40:37Z

New page: '''Unreleased structure''' The entry 5x2s is ON HOLD Authors: Ohki, M., Park, S.-Y. Description: Direct Observation of Conformational Population Shifts in Hemoglobin: Crystal Structure...

New page

'''Unreleased structure'''

The entry 5x2s is ON HOLD

Authors: Ohki, M., Park, S.-Y.

Description: Direct Observation of Conformational Population Shifts in Hemoglobin: Crystal Structure of Half-Liganded Hemoglobin after Adding 4 mM bezafibrate pH 6.5.
[[Category: Unreleased Structures]]
[[Category: Ohki, M]]
[[Category: Park, S.-Y]]