6nbc - Revision history

OCA at 09:20, 20 March 2024

OCA — Wed, 20 Mar 2024 09:20:59 GMT

←Older revision		Revision as of 09:20, 20 March 2024
Line 3:		Line 3:
	<SX load='6nbc' size='340' side='right' viewer='molstar' caption='[[6nbc]], [[Resolution\|resolution]] 2.80Å' scene=''>		<SX load='6nbc' size='340' side='right' viewer='molstar' caption='[[6nbc]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nbc]] 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=6NBC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6NBC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nbc]] 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=6NBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NBC 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">Electron Microscopy, [[Resolution\|Resolution]] 2.8Å</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=6nbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbc OCA], [~~http~~://pdbe.org/6nbc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nbc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nbc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbc 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=6nbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbc OCA], [https://pdbe.org/6nbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nbc RCSB], [https://www.ebi.ac.uk/pdbsum/6nbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbc 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 ==~~	+
-	Determining high-resolution structures of biological macromolecules amassing less than 100 kilodaltons (kDa) has been a longstanding goal of the cryo-electron microscopy (cryo-EM) community. While the Volta phase plate has enabled visualization of specimens in this size range, this instrumentation is not yet fully automated and can present technical challenges. Here, we show that conventional defocus-based cryo-EM methodologies can be used to determine high-resolution structures of specimens amassing less than 100 kDa using a transmission electron microscope operating at 200 keV coupled with a direct electron detector. Our ~2.7 A structure of alcohol dehydrogenase (82 kDa) proves that bound ligands can be resolved with high fidelity to enable investigation of drug-target interactions. Our ~2.8 A and ~3.2 A structures of methemoglobin demonstrate that distinct conformational states can be identified within a dataset for proteins as small as 64 kDa. Furthermore, we provide the sub-nanometer cryo-EM structure of a sub-50 kDa protein.	+
-		+
-	High-resolution structure determination of sub-100 kDa complexes using conventional cryo-EM.,Herzik MA Jr, Wu M, Lander GC Nat Commun. 2019 Mar 4;10(1):1032. doi: 10.1038/s41467-019-08991-8. PMID:30833564<ref>PMID:30833564</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6nbc" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 29:		Line 21:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Herzik~~, M A~~]]	+	[[Category: Herzik Jr MA]]
-	[[Category: Lander~~, G C~~]]	+	[[Category: Lander GC]]
-	[[Category: Wu, M]]	+	[[Category: Wu M]]
-	~~[[Category: Globin]]~~	+
-	~~[[Category: Heme-binding]]~~	+
-	~~[[Category: Hetero-4-mer]]~~	+
-	~~[[Category: Oxygen transport~~]]	+

OCA at 03:16, 11 April 2020

OCA — Sat, 11 Apr 2020 03:16:46 GMT

←Older revision		Revision as of 03:16, 11 April 2020
Line 3:		Line 3:
	<SX load='6nbc' size='340' side='right' viewer='molstar' caption='[[6nbc]], [[Resolution\|resolution]] 2.80Å' scene=''>		<SX load='6nbc' size='340' side='right' viewer='molstar' caption='[[6nbc]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nbc]] 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=6NBC OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NBC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nbc]] 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=6NBC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NBC 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></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></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=6nbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbc OCA], [http://pdbe.org/6nbc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nbc RCSB], [http://www.ebi.ac.uk/pdbsum/6nbc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbc 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=6nbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbc OCA], [http://pdbe.org/6nbc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nbc RCSB], [http://www.ebi.ac.uk/pdbsum/6nbc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbc ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 22:48, 6 March 2020

OCA — Fri, 06 Mar 2020 22:48:45 GMT

←Older revision		Revision as of 22:48, 6 March 2020
Line 1:		Line 1:

	==human methemoglobin state 1 determined using single-particle cryo-EM at 200 keV==		==human methemoglobin state 1 determined using single-particle cryo-EM at 200 keV==
-	<~~StructureSection~~ load='6nbc' size='340' side='right'caption='[[6nbc]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<SX load='6nbc' size='340' side='right' viewer='molstar' caption='[[6nbc]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6nbc]] 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=6NBC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NBC FirstGlance]. <br>		<table><tr><td colspan='2'>[[6nbc]] 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=6NBC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NBC FirstGlance]. <br>
Line 26:		Line 26:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 11:23, 18 December 2019

OCA — Wed, 18 Dec 2019 11:23:51 GMT

←Older revision		Revision as of 11:23, 18 December 2019
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 6nbc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6nbc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Hemoglobin 3D structures\|Hemoglobin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:28, 20 March 2019

OCA — Wed, 20 Mar 2019 08:28:36 GMT

←Older revision		Revision as of 08:28, 20 March 2019
Line 11:		Line 11:
	== 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 ==
		+	Determining high-resolution structures of biological macromolecules amassing less than 100 kilodaltons (kDa) has been a longstanding goal of the cryo-electron microscopy (cryo-EM) community. While the Volta phase plate has enabled visualization of specimens in this size range, this instrumentation is not yet fully automated and can present technical challenges. Here, we show that conventional defocus-based cryo-EM methodologies can be used to determine high-resolution structures of specimens amassing less than 100 kDa using a transmission electron microscope operating at 200 keV coupled with a direct electron detector. Our ~2.7 A structure of alcohol dehydrogenase (82 kDa) proves that bound ligands can be resolved with high fidelity to enable investigation of drug-target interactions. Our ~2.8 A and ~3.2 A structures of methemoglobin demonstrate that distinct conformational states can be identified within a dataset for proteins as small as 64 kDa. Furthermore, we provide the sub-nanometer cryo-EM structure of a sub-50 kDa protein.
		+
		+	High-resolution structure determination of sub-100 kDa complexes using conventional cryo-EM.,Herzik MA Jr, Wu M, Lander GC Nat Commun. 2019 Mar 4;10(1):1032. doi: 10.1038/s41467-019-08991-8. PMID:30833564<ref>PMID:30833564</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6nbc" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:16, 13 March 2019

OCA — Wed, 13 Mar 2019 12:16:25 GMT

←Older revision		Revision as of 12:16, 13 March 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nbc is ~~ON HOLD~~	+	==human methemoglobin state 1 determined using single-particle cryo-EM at 200 keV==
-		+	<StructureSection load='6nbc' size='340' side='right'caption='[[6nbc]], [[Resolution\|resolution]] 2.80Å' scene=''>
-	~~Authors~~: ~~Herzik Jr~~., M.A., Wu, M., ~~Lander~~, G.C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6nbc]] 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=6NBC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NBC FirstGlance]. <br>
-	~~Description~~: ~~human methemoglobin state 1 determined using single~~-~~particle cryo~~-~~EM at 200 keV~~	+	</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></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6nbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbc OCA], [http://pdbe.org/6nbc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nbc RCSB], [http://www.ebi.ac.uk/pdbsum/6nbc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbc 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: Large Structures]]
		+	[[Category: Herzik, M A]]
		+	[[Category: Lander, G C]]
	[[Category: Wu, M]]		[[Category: Wu, M]]
-	[[Category: ~~Herzik Jr~~]]	+	[[Category: Globin]]
-	[[Category: ~~Lander, G.C~~]]	+	[[Category: Heme-binding]]
-	[[Category: ~~M.A~~]]	+	[[Category: Hetero-4-mer]]
		+	[[Category: Oxygen transport]]

OCA: Protected "6nbc" [edit=sysop:move=sysop]

OCA — Wed, 12 Dec 2018 05:28:10 GMT

Protected "6nbc" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:28, 12 December 2018

OCA: New page: '''Unreleased structure''' The entry 6nbc is ON HOLD Authors: Herzik Jr., M.A., Wu, M., Lander, G.C. Description: human methemoglobin state 1 determined using single-particle cryo-EM a...

OCA — Wed, 12 Dec 2018 05:28:09 GMT

New page: '''Unreleased structure''' The entry 6nbc is ON HOLD Authors: Herzik Jr., M.A., Wu, M., Lander, G.C. Description: human methemoglobin state 1 determined using single-particle cryo-EM a...

New page

'''Unreleased structure'''

The entry 6nbc is ON HOLD

Authors: Herzik Jr., M.A., Wu, M., Lander, G.C.

Description: human methemoglobin state 1 determined using single-particle cryo-EM at 200 keV
[[Category: Unreleased Structures]]
[[Category: Wu, M]]
[[Category: Herzik Jr]]
[[Category: Lander, G.C]]
[[Category: M.A]]