This title appears in the Scientific Report :
2008
Please use the identifier:
http://dx.doi.org/10.1002/cbic.200800117 in citations.
An indole binding site is a major determinant of the ligand specificity of the GABA type A receptor-associated protein GABARAP
An indole binding site is a major determinant of the ligand specificity of the GABA type A receptor-associated protein GABARAP
The role of tryptophan as a key residue for ligand binding to the ubiquitin-like modifier GABA(A) receptor associated protein (GABARAP) was investigated. Two tryptophan-binding hydrophobic patches were identified on the conserved face of the GABARAP structure by NMR spectroscopy and molecular dockin...
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Personal Name(s): | Thielmann, Y. |
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Mohrlüder, J. / Koenig, B. W. / Stangler, T. / Hartmann, R. / Becker, K. / Höltje, H.-D. / Willbold, D. | |
Contributing Institute: |
Molekulare Biophysik; INB-2 |
Published in: | ChemBioChem, 9 (2008) S. 1767 - 1775 |
Imprint: |
Weinheim
Wiley-VCH
2008
|
Physical Description: |
1767 - 1775 |
DOI: |
10.1002/cbic.200800117 |
PubMed ID: |
18567048 |
Document Type: |
Journal Article |
Research Program: |
Funktion und Dysfunktion des Nervensystems |
Series Title: |
ChemBioChem
9 |
Subject (ZB): | |
Publikationsportal JuSER |
The role of tryptophan as a key residue for ligand binding to the ubiquitin-like modifier GABA(A) receptor associated protein (GABARAP) was investigated. Two tryptophan-binding hydrophobic patches were identified on the conserved face of the GABARAP structure by NMR spectroscopy and molecular docking. GABARAP binding of indole and indole derivatives, including the free amino acid tryptophan was quantified. The two tryptophan binding sites can be clearly distinguished by mapping the NMR spectroscopy-derived residue-specific apparent dissociation constant, K(d), onto the three-dimensional structure of GABARAP. The biological relevance of tryptophan-binding pockets of GABARAP was supported by a highly conserved tryptophan residue in the GABARAP binding region of calreticulin, clathrin heavy chain, and the gamma2 subunit of the GABA(A) receptor. Replacement of tryptophan by alanine abolished ligand binding to GABARAP. |