Purification and Spectroscopic Characterization of the Human Protein Tyrosine Kinase-6 SH3 Domain

Koo, Bon Kyung; Kim, Min Hyung; Lee, Seung Taek; Lee, Weontae

doi:10.5483/bmbrep.2002.35.3.343

Cited by 5 publications

(3 citation statements)

References 19 publications

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“…CD spectra were recorded from 190 to 250 nm at a scanning rate of 50 nm/min with a time constant of 0.5 sec. Each CD spectrum was obtained by averaging 10 recordings with a step resolution of 0.2 nm and a bandwidth of 2.0 nm in cells with 0.1 mm path length (Koo et al, 2002). NMR spectroscopy NMR was performed upon 2 mM of the peptide in 50 mM potassium phosphate buffer at pH 7.0 in 100% D 2 O and 90% H 2 O/10% D 2 O. NMR spectra were recorded at 278 K on Bruker DRX-500 and DRX-600 spectrometers equipped with a triple-resonance probe and an x, y, z-shielded pulsed-field gradient coil.…”

Section: Methodsmentioning

confidence: 99%

Solution Structure of Human Orexin-A: Regulator of Appetite and Wakefulness

Kim

Hong

Kim³

et al. 2004

BMB Reports

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Orexin-A and orexin-B (hypocretin-1 and hypocretin-2, respectively) are important hypothalamic neuro-peptides, which are encoded by a single mRNA transcript and stimulate food intake as well as regulate wakefulness. Here we determined the solution structure of orexin-A by NMR spectroscopy and by simulated-annealing calculation. The structural features of orexin-A involve two alpha-helices, with the hydrophobic residues disposed to on one side of helix, and hydrophilic residues to the other. A hydrophilic turn induced by two disulfide bonds provides the key difference between orexin-A and -B. With previous mutagenic studies, the derived structure of orexin-A provides us with a structure-functional view for novel drug design.

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Section: Methodsmentioning

confidence: 99%

Solution Structure of Human Orexin-A: Regulator of Appetite and Wakefulness

Kim

Hong

Kim³

et al. 2004

BMB Reports

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“…Interactions between the SH3 domain and the proline-rich linker region are also involved in autoinhibition [16,19,20] and are thought to stabilize the inactive state of the enzyme similar to SRC. The SH3 domain consists mainly of β-sheets, which exhibit a unique and folded structure at neutral pH that is sensitive to pH changes [21]. Aside from intramolecular interactions [19,20], the SH3 domain of PTK6 plays a major role in substrate interactions [18,22–24].…”

Section: Ptk6 Structurementioning

confidence: 99%

Building a better understanding of the intracellular tyrosine kinase PTK6 — BRK by BRK

Brauer

Tyner

2010

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

130

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Protein tyrosine kinase 6 (PTK6), also referred to as breast tumor kinase BRK, is a member of a distinct family of kinases that is evolutionarily related to the SRC family of tyrosine kinases. While not expressed in the normal mammary gland, PTK6 expression is detected in a large proportion of human mammary gland tumors. In breast tumor cells, PTK6 promotes growth factor signaling and cell migration. PTK6 expression is also increased in a number of other epithelial tumors, including ovarian and colon cancer. In contrast, PTK6 is expressed in diverse normal epithelia, including the linings of the gastrointestinal tract, skin and prostate, where its expression correlates with cell cycle exit and differentiation. Disruption of the mouse Ptk6 gene leads to increased growth and impaired differentiation in the small intestine that is accompanied by increased AKT and Wnt signaling. Following total body irradiation, PTK6 expression is induced in proliferating progenitor cells of the intestine, where it plays an essential role in DNA-damage induced apoptosis. A distinguishing feature of PTK6 is its flexibility in intracellular localization, due to a lack of amino-terminal myristoylation/ palmitoylation. Recently a number of substrates of PTK6 have been identified, including nuclear RNA-binding proteins and transcription factors. We discuss PTK6 signaling, its apparent conflicting roles in cancer and normal epithelia, and its potential as a therapeutic target in epithelial cancers.

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“…NMR spectroscopy For the NMR experiments, all of the samples were dissolved in DMSO-d 6 (Cambridge Isotope Inc.) at a concentration of 2 mM. The NMR measurements were performed at 25 o C with a 500 MHz Bruker DRX500 spectrometer that was equipped with a SGI workstation as described our previous research (Koo et al, 2002). Data were collected with a 7002 Hz spectral width, 2048 complex points in t 2 and 128 increments in t 1 for 1 H-1 H two-dimensional total correlation spectroscopy (TOCSY) with a mixing time of 69 ms (Davis and Bax, 1985) and for 1H-1H twodimensional rotating frame nuclear Overhauser enhancement spectroscopy (ROESY) experiments .…”

Section: Methodsmentioning

confidence: 99%

NMR Studies on Turn Mimetic Analogs Derived from Melanocyte-stimulating Hormones

Cho¹,

Kim²,

Lee³

et al. 2003

BMB Reports

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Oligomers with alpha-aminooxy acids are reported to form very stable turn and helix structures, and they are supposed to be useful peptidomimetics for drug design. A recent report suggested that homochiral oxa-peptides form a strong eight-member-ring structure by a hydrogen bond between adjacent aminooxy-acid residues in a CDCl3 solution. In order to design an alpha-MSH analog with a stable turn conformation, we synthesized four tetramers and one pentamer, based on alpha-MSH sequence, and determined the solution structures of the molecules by two-dimensional NMR spectroscopy and simulated annealing calculations. The solution conformations of the three peptidomimetic molecules (TLV, TDV, and TLL) in DMSO-d6 contain a stable 7-membered-ring structure that is similar to a gamma-turn in normal peptides. Newly-designed tetramer TDF and pentamer PDF have a ball-type rigid structure that is induced by strong hydrogen bonds between adjacent amide protons and carbonyl oxygens. In conclusion, the aminooxy acids, easily prepared from natural or unnatural amino acids, can be employed to prepare peptidomimetic analogues with well-defined turn structures for pharmaceutical interest.

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Purification and Spectroscopic Characterization of the Human Protein Tyrosine Kinase-6 SH3 Domain

Cited by 5 publications

References 19 publications

Solution Structure of Human Orexin-A: Regulator of Appetite and Wakefulness

Solution Structure of Human Orexin-A: Regulator of Appetite and Wakefulness

Building a better understanding of the intracellular tyrosine kinase PTK6 — BRK by BRK

NMR Studies on Turn Mimetic Analogs Derived from Melanocyte-stimulating Hormones

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