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==IMMUNOGLOBULIN LAMBDA LIGHT CHAIN DIMER (MCG) COMPLEX WITH ASPARTAME== | |||
<StructureSection load='1a8j' size='340' side='right'caption='[[1a8j]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
| | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1a8j]] is a 2 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=1A8J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A8J 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]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=PME:N-L-ALPHA-ASPARTYL+L-PHENYLALANINE+1-METHYL+ESTER'>PME</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=1a8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a8j OCA], [https://pdbe.org/1a8j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a8j RCSB], [https://www.ebi.ac.uk/pdbsum/1a8j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a8j ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LV208_HUMAN LV208_HUMAN] V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref> <ref>PMID:24600447</ref> | |||
== 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/a8/1a8j_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1a8j ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
OBJECTIVE: The binding of sweet-tasting compounds in a human (Mcg) Bence-Jones dimer has been characterized by x-ray crystallography. Aspartame binding in this immunoglobulin fragment is remarkable. Unexpected pain relief noted by A.B.E., a crystallographer with diagnosed osteoarthritis, suggested that the accommodation of aspartame in the active site of the dimer may represent surrogate binding by other proteins, with analgesia as the outcome. METHODS: X-ray analysis of the complex of aspartame and the Bence-Jones dimer was conducted with crystalline Mcg protein and pure aspartame. A single-blind (n = 1) study to confirm analgesia was completed by administration of aspartame to A.B.E. A controlled double-blind trial was performed in patients with x-ray-documented osteoarthritis. Pain and performance changes were evaluated with use of two doses of placebo and two doses of aspartame. Effects on bleeding time were then evaluated by determination of template bleeding times in 34 normal volunteers. Finally, antipyretic effects were studied in Sprague-Dawley rats given intramuscular turpentine injections. RESULTS: Aspartame binding in the Bence-Jones dimer was verified by x-ray crystallography. Improvements in performance and pain relief were observed in A.B.E. at p < 0.001. Decreased pain and improved performance were also observed in patients with osteoarthritis (p < 0.001). Mild antihemostatic responses were observed in bleeding times after aspartame treatment. Modified template bleeding times increased at p < 0.01. Aspartame blocked the turpentine-mediated febrile responses in the treated rats (p < 0.01). CONCLUSIONS: L-Aspartyl-L-phenylalanine methyl ester is biologically active and appears to relieve pain, induce mild antithrombotic effects in humans, and decrease fever in animals. | OBJECTIVE: The binding of sweet-tasting compounds in a human (Mcg) Bence-Jones dimer has been characterized by x-ray crystallography. Aspartame binding in this immunoglobulin fragment is remarkable. Unexpected pain relief noted by A.B.E., a crystallographer with diagnosed osteoarthritis, suggested that the accommodation of aspartame in the active site of the dimer may represent surrogate binding by other proteins, with analgesia as the outcome. METHODS: X-ray analysis of the complex of aspartame and the Bence-Jones dimer was conducted with crystalline Mcg protein and pure aspartame. A single-blind (n = 1) study to confirm analgesia was completed by administration of aspartame to A.B.E. A controlled double-blind trial was performed in patients with x-ray-documented osteoarthritis. Pain and performance changes were evaluated with use of two doses of placebo and two doses of aspartame. Effects on bleeding time were then evaluated by determination of template bleeding times in 34 normal volunteers. Finally, antipyretic effects were studied in Sprague-Dawley rats given intramuscular turpentine injections. RESULTS: Aspartame binding in the Bence-Jones dimer was verified by x-ray crystallography. Improvements in performance and pain relief were observed in A.B.E. at p < 0.001. Decreased pain and improved performance were also observed in patients with osteoarthritis (p < 0.001). Mild antihemostatic responses were observed in bleeding times after aspartame treatment. Modified template bleeding times increased at p < 0.01. Aspartame blocked the turpentine-mediated febrile responses in the treated rats (p < 0.01). CONCLUSIONS: L-Aspartyl-L-phenylalanine methyl ester is biologically active and appears to relieve pain, induce mild antithrombotic effects in humans, and decrease fever in animals. | ||
Treatment of osteoarthritis with aspartame.,Edmundson AB, Manion CV Clin Pharmacol Ther. 1998 May;63(5):580-93. PMID:9630831<ref>PMID:9630831</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1a8j" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Edmundson | [[Category: Edmundson AB]] | ||
[[Category: Manion | [[Category: Manion CV]] | ||