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@ARTICLE{Schmidt:55440,
author = {Schmidt, H. and Hoffmann, S. and Tran, T. and Stoldt, M.
and Stangler, T. and Wiesehan, K. and Willbold, D.},
title = {{S}olution structure of a {H}ck {SH}3 domain ligand complex
reveals novel interaction modes},
journal = {Journal of molecular biology},
volume = {365},
issn = {0022-2836},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {PreJuSER-55440},
pages = {1517 - 1532},
year = {2007},
note = {Record converted from VDB: 12.11.2012},
abstract = {We studied the interaction of hematopoietic cell kinase SH3
domain (HckSH3) with an artificial 12-residue proline-rich
peptide PD1 (HSKYPLPPLPSL) identified as high affinity
ligand (K(D)=0.2 muM). PD1 shows an unusual ligand sequence
for SH3 binding in type I orientation because it lacks the
typical basic anchor residue at position P(-3), but instead
has a tyrosine residue at this position. A basic lysine
residue, however, is present at position P(-4). The solution
structure of the HckSH3:PD1 complex, which is the first
HckSH3 complex structure available, clearly reveals that the
P(-3) tyrosine residue of PD1 does not take the position of
the typical anchor residue but rather forms additional van
der Waals interactions with the HckSH3 RT loop. Instead,
lysine at position P(-4) of PD1 substitutes the function of
the P(-3) anchor residue. This finding expands the well
known ligand consensus sequence +xxPpxP by +xxxPpxP. Thus,
software tools like iSPOT fail to identify PD1 as a
high-affinity HckSH3 ligand so far. In addition, a short
antiparallel beta-sheet in the RT loop of HckSH3 is observed
upon PD1 binding. The structure of the HckSH3:PD1 complex
reveals novel features of SH3 ligand binding and yields new
insights into the structural basics of SH3-ligand
interactions. Consequences for computational prediction
tools adressing SH3-ligand interactions as well as the
biological relevance of our findings are discussed.},
keywords = {Amides / Amino Acid Sequence / Binding Sites / Deuterium
Oxide: metabolism / Half-Life / Humans / Kinetics / Ligands
/ Models, Molecular / Molecular Sequence Data / Nuclear
Magnetic Resonance, Biomolecular / Peptide Mapping /
Peptides: chemistry / Peptides: metabolism / Protein Binding
/ Proto-Oncogene Proteins c-hck: analysis / Proto-Oncogene
Proteins c-hck: chemistry / Proto-Oncogene Proteins c-hck:
metabolism / Protons / Solutions / Water: metabolism / src
Homology Domains / Amides (NLM Chemicals) / Ligands (NLM
Chemicals) / Peptides (NLM Chemicals) / Protons (NLM
Chemicals) / Solutions (NLM Chemicals) / Water (NLM
Chemicals) / Deuterium Oxide (NLM Chemicals) / HCK protein,
human (NLM Chemicals) / Proto-Oncogene Proteins c-hck (NLM
Chemicals) / J (WoSType)},
cin = {INB-2 / JARA-SIM},
ddc = {570},
cid = {I:(DE-Juel1)VDB805 / I:(DE-Juel1)VDB1045},
pnm = {Funktion und Dysfunktion des Nervensystems},
pid = {G:(DE-Juel1)FUEK409},
shelfmark = {Biochemistry $\&$ Molecular Biology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:17141806},
UT = {WOS:000243749600023},
doi = {10.1016/j.jmb.2006.11.013},
url = {https://juser.fz-juelich.de/record/55440},
}