1ynk: Difference between revisions
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==Identification of Key residues of the NC6.8 Fab antibody fragment binding to synthetic sweeteners: Crystal structure of NC6.8 co-crystalized with high potency sweetener compound SC45647== | |||
<StructureSection load='1ynk' size='340' side='right'caption='[[1ynk]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1ynk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YNK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YNK 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SC5:2-[((R)-{[4-(AMINOMETHYL)PHENYL]AMINO}{[(1R)-1-PHENYLETHYL]AMINO}METHYL)AMINO]ETHANE-1,1-DIOL'>SC5</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=1ynk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ynk OCA], [https://pdbe.org/1ynk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ynk RCSB], [https://www.ebi.ac.uk/pdbsum/1ynk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ynk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A2P1G9_MOUSE A2P1G9_MOUSE] | |||
== 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/yn/1ynk_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=1ynk ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The crystal structures of the murine monoclonal IgG2b(kappa) antibody NC6.8 Fab fragment complexed with high-potency sweetener compound SC45647 and nontasting high-affinity antagonist TES have been determined. The crystal structures show how sweetener potency is fine-tuned by multiple interactions between specific receptor residues and the functionally different groups of the sweeteners. Comparative analysis with the structure of NC6.8 complexed with the super-potency sweetener NC174 reveals that although the same residues in the antigen binding pocket of NC6.8 interact with the zwitterionic, trisubstituted guanidinium sweeteners as well as TES, specific differences exist and provide guidance for the design of new artificial sweeteners. In case of the nonsweetener TES, the interactions with the receptor are indirectly mediated through a hydrogen bonded water network, while the sweeteners bind with high affinity directly to the receptor. The presence of a hydrophobic group interacting with multiple receptor residues as a major determinant for sweet taste has been confirmed. The nature of the hydrophobic group is likely a discriminator for super- versus high-potency sweeteners, which can be exploited in the design of new, highly potent sweetener compounds. Overall similarities and partial conservation of interactions indicate that the NC6.8 Fab surrogate is representing crucial features of the T1R2 taste receptor VFTM binding site. | |||
Cocrystal structures of NC6.8 Fab identify key interactions for high potency sweetener recognition: implications for the design of synthetic sweeteners.,Gokulan K, Khare S, Ronning DR, Linthicum SD, Sacchettini JC, Rupp B Biochemistry. 2005 Jul 26;44(29):9889-98. PMID:16026161<ref>PMID:16026161</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1ynk" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Antibody|Antibody]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== | *[[3D structures of non-human antibody|3D structures of non-human antibody]] | ||
< | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Gokulan | [[Category: Gokulan K]] | ||
[[Category: Khare | [[Category: Khare S]] | ||
[[Category: Linthicum | [[Category: Linthicum SD]] | ||
[[Category: Ronning | [[Category: Ronning DR]] | ||
[[Category: Rupp | [[Category: Rupp B]] | ||
[[Category: Sacchettini | [[Category: Sacchettini JC]] | ||
Latest revision as of 09:59, 23 August 2023
Identification of Key residues of the NC6.8 Fab antibody fragment binding to synthetic sweeteners: Crystal structure of NC6.8 co-crystalized with high potency sweetener compound SC45647Identification of Key residues of the NC6.8 Fab antibody fragment binding to synthetic sweeteners: Crystal structure of NC6.8 co-crystalized with high potency sweetener compound SC45647
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe crystal structures of the murine monoclonal IgG2b(kappa) antibody NC6.8 Fab fragment complexed with high-potency sweetener compound SC45647 and nontasting high-affinity antagonist TES have been determined. The crystal structures show how sweetener potency is fine-tuned by multiple interactions between specific receptor residues and the functionally different groups of the sweeteners. Comparative analysis with the structure of NC6.8 complexed with the super-potency sweetener NC174 reveals that although the same residues in the antigen binding pocket of NC6.8 interact with the zwitterionic, trisubstituted guanidinium sweeteners as well as TES, specific differences exist and provide guidance for the design of new artificial sweeteners. In case of the nonsweetener TES, the interactions with the receptor are indirectly mediated through a hydrogen bonded water network, while the sweeteners bind with high affinity directly to the receptor. The presence of a hydrophobic group interacting with multiple receptor residues as a major determinant for sweet taste has been confirmed. The nature of the hydrophobic group is likely a discriminator for super- versus high-potency sweeteners, which can be exploited in the design of new, highly potent sweetener compounds. Overall similarities and partial conservation of interactions indicate that the NC6.8 Fab surrogate is representing crucial features of the T1R2 taste receptor VFTM binding site. Cocrystal structures of NC6.8 Fab identify key interactions for high potency sweetener recognition: implications for the design of synthetic sweeteners.,Gokulan K, Khare S, Ronning DR, Linthicum SD, Sacchettini JC, Rupp B Biochemistry. 2005 Jul 26;44(29):9889-98. PMID:16026161[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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