1ynk
From Proteopedia
(New page: 200px<br /> <applet load="1ynk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ynk, resolution 2.10Å" /> '''Identification of K...) |
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| - | [[Image:1ynk.gif|left|200px]]<br /> | + | [[Image:1ynk.gif|left|200px]]<br /><applet load="1ynk" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ynk" size=" | + | |
caption="1ynk, resolution 2.10Å" /> | caption="1ynk, resolution 2.10Å" /> | ||
'''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'''<br /> | '''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'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structures of the murine monoclonal IgG2b(kappa) antibody | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1YNK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SC5 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1YNK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SC5:'>SC5</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YNK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Gokulan, K.]] | [[Category: Gokulan, K.]] | ||
[[Category: Khare, S.]] | [[Category: Khare, S.]] | ||
| - | [[Category: Linthicum, S | + | [[Category: Linthicum, S D.]] |
| - | [[Category: Ronning, D | + | [[Category: Ronning, D R.]] |
[[Category: Rupp, B.]] | [[Category: Rupp, B.]] | ||
| - | [[Category: Sacchettini, J | + | [[Category: Sacchettini, J C.]] |
[[Category: SC5]] | [[Category: SC5]] | ||
[[Category: sc45657 and nc174]] | [[Category: sc45657 and nc174]] | ||
[[Category: sweetener compound]] | [[Category: sweetener compound]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:07:13 2008'' |
Revision as of 14:07, 21 February 2008
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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
Overview
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.
About this Structure
1YNK is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
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
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