View source for 8vyl


==The structure of Human Hemoglobin in Complex with Nanobody BtNbE11==
<StructureSection load='8vyl' size='340' side='right'caption='[[8vyl]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vyl]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VYL 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]] 2.02&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</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'>[https://proteopedia.org/fgij/fg.htm?mol=8vyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vyl OCA], [https://pdbe.org/8vyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vyl RCSB], [https://www.ebi.ac.uk/pdbsum/8vyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vyl 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Haemoglobin (Hb) is a vital oxygen carrier in vertebrates. Low blood Hb levels may indicate anaemia or genetic disorders, while its presence in the lower digestive system suggests colon cancer. Detecting and quantifying human Hb is essential for medical diagnostics. A nanobody-based sandwich-ELISA test was recently developed utilising llama-derived nanobodies NbE11 and NbB9. These nanobodies specifically bind to human Hb without cross-reacting with Hb from other vertebrates. Here, we determine the crystal structure of NbE11 in complex with human Hb. NbE11 binds Hb with high affinity, predominantly binding the beta-Hb subunit. Structural differences between human Hb and other vertebrates at the NbE11 binding interface likely explain the assay's lack of cross-reactivity, providing insights for developing Hb binding diagnostics.

The structure of a haemoglobin-nanobody complex reveals human beta-subunit-specific interactions.,Fox DR, Samuels I, Binks S, Grinter R FEBS Lett. 2024 Jun 16. doi: 10.1002/1873-3468.14958. PMID:38880764<ref>PMID:38880764</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vyl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Binks S]]
[[Category: Fox D]]
[[Category: Grinter R]]