PDBsum entry 1ynl

Immune system

PDB id: 1ynl

Contents

Protein chains

219 a.a. *

219 a.a. *

Ligands

NES

Waters ×347

* Residue conservation analysis

PDB id:

1ynl

Name:

Immune system

Title:

Identification of key residues of the nc6.8 fab antibody fragment binding to synthetic sweeterners: crystal structure of nc6.8 co- crystalized with high potency sweetener compound sc45647

Structure:

Ig gamma light chain. Chain: l. Synonym: monoclonal antibody fab fragment. Engineered: yes. Ig gamma heavy chain. Chain: h. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090

Biol. unit:

Dimer (from PQS)

Resolution:

1.70Å R-factor: 0.208 R-free: 0.241

Authors:

K.Gokulan,S.Khare,D.R.Ronning,S.D.Linthicum,J.C.Sacchettini,B.Rupp

Key ref:

K.Gokulan et al. (2005). Cocrystal structures of NC6.8 Fab identify key interactions for high potency sweetener recognition: implications for the design of synthetic sweeteners. Biochemistry, 44, 9889-9898. PubMed id: 16026161 DOI: 10.1021/bi050613u

Date:

24-Jan-05 Release date: 16-Aug-05

Protein chain

A2P1G9  (A2P1G9_MOUSE) -  Kappa light chain (Fragment) from Mus musculus

Seq: 219 a.a.

Struc: 219 a.a.*

Protein chain

Q6PJB2  (Q6PJB2_MOUSE) -  Igh protein from Mus musculus

Seq: 465 a.a.

Struc: 219 a.a.*

* PDB and UniProt seqs differ at 61 residue positions (black crosses)

DOI no: 10.1021/bi050613u

Biochemistry 44:9889-9898 (2005)

PubMed id: 16026161

Cocrystal structures of NC6.8 Fab identify key interactions for high potency sweetener recognition: implications for the design of synthetic sweeteners.

K.Gokulan, S.Khare, D.R.Ronning, S.D.Linthicum, J.C.Sacchettini, B.Rupp.

ABSTRACT

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.