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@ARTICLE{Thielmann:62893,
author = {Thielmann, Y. and Mohrlüder, J. and Koenig, B. W. and
Stangler, T. and Hartmann, R. and Becker, K. and Höltje,
H.-D. and Willbold, D.},
title = {{A}n indole binding site is a major determinant of the
ligand specificity of the {GABA} type {A}
receptor-associated protein {GABARAP}},
journal = {ChemBioChem},
volume = {9},
issn = {1439-4227},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {PreJuSER-62893},
pages = {1767 - 1775},
year = {2008},
note = {Record converted from VDB: 12.11.2012},
abstract = {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.},
keywords = {Adaptor Proteins, Signal Transducing: chemistry / Adaptor
Proteins, Signal Transducing: metabolism / Amino Acid
Sequence / Animals / Binding Sites / Humans / Hydrophobic
and Hydrophilic Interactions / Indoles: chemistry / Indoles:
metabolism / Ligands / Microtubule-Associated Proteins:
chemistry / Microtubule-Associated Proteins: metabolism /
Models, Molecular / Molecular Sequence Data / Protein
Conformation / Receptors, GABA-A: metabolism / Substrate
Specificity / Titrimetry / Tryptophan: metabolism / Adaptor
Proteins, Signal Transducing (NLM Chemicals) / Indoles (NLM
Chemicals) / Ligands (NLM Chemicals) /
Microtubule-Associated Proteins (NLM Chemicals) / Receptors,
GABA-A (NLM Chemicals) / Tryptophan (NLM Chemicals) / J
(WoSType)},
cin = {INB-2},
ddc = {540},
cid = {I:(DE-Juel1)VDB805},
pnm = {Funktion und Dysfunktion des Nervensystems},
pid = {G:(DE-Juel1)FUEK409},
shelfmark = {Biochemistry $\&$ Molecular Biology / Chemistry, Medicinal},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:18567048},
UT = {WOS:000258092300014},
doi = {10.1002/cbic.200800117},
url = {https://juser.fz-juelich.de/record/62893},
}