TY  - JOUR
AU  - Thielmann, Y.
AU  - Mohrlüder, J.
AU  - Koenig, B. W.
AU  - Stangler, T.
AU  - Hartmann, R.
AU  - Becker, K.
AU  - Höltje, H.-D.
AU  - Willbold, D.
TI  - An indole binding site is a major determinant of the ligand specificity of the GABA type A receptor-associated protein GABARAP
JO  - ChemBioChem
VL  - 9
SN  - 1439-4227
CY  - Weinheim
PB  - Wiley-VCH
M1  - PreJuSER-62893
SP  - 1767 - 1775
PY  - 2008
N1  - Record converted from VDB: 12.11.2012
AB  - 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.
KW  - Adaptor Proteins, Signal Transducing: chemistry
KW  - Adaptor Proteins, Signal Transducing: metabolism
KW  - Amino Acid Sequence
KW  - Animals
KW  - Binding Sites
KW  - Humans
KW  - Hydrophobic and Hydrophilic Interactions
KW  - Indoles: chemistry
KW  - Indoles: metabolism
KW  - Ligands
KW  - Microtubule-Associated Proteins: chemistry
KW  - Microtubule-Associated Proteins: metabolism
KW  - Models, Molecular
KW  - Molecular Sequence Data
KW  - Protein Conformation
KW  - Receptors, GABA-A: metabolism
KW  - Substrate Specificity
KW  - Titrimetry
KW  - Tryptophan: metabolism
KW  - Adaptor Proteins, Signal Transducing (NLM Chemicals)
KW  - Indoles (NLM Chemicals)
KW  - Ligands (NLM Chemicals)
KW  - Microtubule-Associated Proteins (NLM Chemicals)
KW  - Receptors, GABA-A (NLM Chemicals)
KW  - Tryptophan (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:18567048
UR  - <Go to ISI:>//WOS:000258092300014
DO  - DOI:10.1002/cbic.200800117
UR  - https://juser.fz-juelich.de/record/62893
ER  -