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@ARTICLE{Gerharz:30967,
author = {Gerharz, T. and Reinelt, S. and Kaspar, S. and Scapozza, L.
and Bott, M.},
title = {{I}dentification of basic amino acid residues important for
citrate binding by the periplasmic receptor domain of the
sensor kinase {C}it{A}},
journal = {Biochemistry},
volume = {42},
issn = {0006-2960},
address = {Columbus, Ohio},
publisher = {American Chemical Society},
reportid = {PreJuSER-30967},
pages = {5917 - 5924},
year = {2003},
note = {Record converted from VDB: 12.11.2012},
abstract = {The sensor kinase CitA and the response regulator CitB of
Klebsiella pneumoniae form the paradigm of a subfamily of
bacterial two-component regulatory systems that are capable
of sensing tri- or dicarboxylates in the environment and
then induce transporters for the uptake of these compounds.
We recently showed that the separated periplasmic domain of
CitA, termed CitAP (encompasses residues 45-176 supplemented
with an N-terminal methionine residue and a C-terminal
hexahistidine tag), is a highly specific citrate receptor
with a K(d) of 5.5 microM at pH 7. To identify positively
charged residues involved in binding the citrate anion, each
of the arginine, lysine, and histidine residues in CitAP was
exchanged for alanine, and the resulting 17 muteins were
analyzed by isothermal titration calorimetry (ITC). In 12
cases, the K(d) for citrate was identical to that of
wild-type CitAP or slightly changed (3.9-17.2 microM). In
one case (R98A), the K(d) was 6-fold decreased (0.8 microM),
whereas in four cases (R66A, H69A, R107A, and K109A) the
K(d) was 38- to >300-fold increased (0.2 to >1 mM). The
secondary structure of the latter five proteins in their
apo-form as deduced from far-UV circular dichroism (CD)
spectra did not differ from the apo-form of wild-type CitAP;
however, all of them showed an increased thermostability.
Citrate increased the melting point (T(m)) of wild-type
CitAP and mutein R98A by 6.2 and 9.5 degrees C,
respectively, but had no effect on the T(m) of the four
proteins with disturbed binding. Three of the residues
important for citrate binding (R66, H69, and R107) are
highly conserved in the CitA subfamily of sensor kinases,
indicating that they might be involved in ligand binding by
many of these sensor kinases.},
keywords = {Amino Acid Sequence / Amino Acid Substitution / Amino
Acids, Basic: chemistry / Bacterial Proteins: chemistry /
Bacterial Proteins: genetics / Bacterial Proteins:
metabolism / Base Sequence / Binding Sites / Circular
Dichroism / Citric Acid: metabolism / DNA, Bacterial:
genetics / Escherichia coli Proteins: chemistry /
Escherichia coli Proteins: genetics / Escherichia coli
Proteins: metabolism / Kinetics / Klebsiella pneumoniae:
genetics / Klebsiella pneumoniae: metabolism / Ligands /
Molecular Sequence Data / Mutagenesis, Site-Directed /
Periplasm: metabolism / Protein Binding / Protein Kinases:
chemistry / Protein Kinases: genetics / Protein Kinases:
metabolism / Protein Structure, Tertiary / Sequence
Homology, Amino Acid / Spectrometry, Mass, Matrix-Assisted
Laser Desorption-Ionization / Thermodynamics / Transcription
Factors: chemistry / Transcription Factors: genetics /
Transcription Factors: metabolism / Amino Acids, Basic (NLM
Chemicals) / Bacterial Proteins (NLM Chemicals) / CitB
protein, Klebsiella pneumoniae (NLM Chemicals) / DNA,
Bacterial (NLM Chemicals) / Escherichia coli Proteins (NLM
Chemicals) / Ligands (NLM Chemicals) / Transcription Factors
(NLM Chemicals) / Citric Acid (NLM Chemicals) / Protein
Kinases (NLM Chemicals) / dpiB protein, E coli (NLM
Chemicals) / J (WoSType)},
cin = {IBT-1},
ddc = {570},
cid = {I:(DE-Juel1)VDB55},
pnm = {Biotechnologie},
pid = {G:(DE-Juel1)FUEK256},
shelfmark = {Biochemistry $\&$ Molecular Biology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:12741850},
UT = {WOS:000182934300041},
doi = {10.1021/bi0340595},
url = {https://juser.fz-juelich.de/record/30967},
}