2d60: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2d60.gif|left|200px]]<br />
-<applet load="2d60" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2d60, resolution 1.70&Aring;" />
-'''Crystal structure of deoxy human hemoglobin complexed with two L35 molecules'''<br />
-==Overview==
+==Crystal structure of deoxy human hemoglobin complexed with two L35 molecules==
-Although detailed crystal structures of haemoglobin (Hb) provide a clear, understanding of the basic allosteric mechanism of the protein, and how, this in turn controls oxygen affinity, recent experiments with artificial, effector molecules have shown a far greater control of oxygen binding than, with natural heterotropic effectors. Contrary to the established text-book, view, these non-physiological compounds are able to reduce oxygen affinity, very strongly without switching the protein to the T (tense) state. In an, earlier paper we showed that bezafibrate (BZF) binds to a surface pocket, on the alpha subunits of R state Hb, strongly reducing the oxygen affinity, of this protein conformation. Here we report the crystallisation of Hb, with L35, a related compound, and show that this binds to the central, cavity of both R and T state Hb. The mechanism by which L35 reduces oxygen, affinity is discussed, in relation to spectroscopic studies of effector, binding.
+<StructureSection load='2d60' size='340' side='right'caption='[[2d60]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2d60]] 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=2D60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2D60 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</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=L35:2-[4-({[(3,5-DICHLOROPHENYL)AMINO]CARBONYL}AMINO)PHENOXY]-2-METHYLPROPANOIC+ACID'>L35</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=2d60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d60 OCA], [https://pdbe.org/2d60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2d60 RCSB], [https://www.ebi.ac.uk/pdbsum/2d60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2d60 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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 ==
+[https://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN] Involved in oxygen transport from the lung to the various peripheral tissues.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d6/2d60_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2d60 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-D60 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HEM and L35 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2D60 OCA].
+*[[Hemoglobin 3D structures|Hemoglobin 3D structures]]
+== References ==
-==Reference==
+<references/>
-R-state haemoglobin with low oxygen affinity: crystal structures of deoxy human and carbonmonoxy horse haemoglobin bound to the effector molecule L35., Yokoyama T, Neya S, Tsuneshige A, Yonetani T, Park SY, Tame JR, J Mol Biol. 2006 Feb 24;356(3):790-801. Epub 2005 Dec 21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16403522 16403522]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Neya, S.]]
+[[Category: Neya S]]
-[[Category: Park, S.Y.]]
+[[Category: Park SY]]
-[[Category: Tame, J.R.]]
+[[Category: Tame JR]]
-[[Category: Tsuneshige, A.]]
+[[Category: Tsuneshige A]]
-[[Category: Yokoyama, T.]]
+[[Category: Yokoyama T]]
-[[Category: Yonetani, T.]]
+[[Category: Yonetani T]]
-[[Category: HEM]]
-[[Category: L35]]
-[[Category: allosteric effector]]
-[[Category: crystal sructure]]
-[[Category: hemoglobin]]
-[[Category: l35]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 13:29:25 2007''