The g-factor shift of the g =
4.1 EPR signal was detected in spinach PsbO/P/Q-depleted PS II. The
effective g-factor of the signal shifts up to ∼4.9,
depending on the Ca2+ concentration. Hyperfine structure
spacing with about 3 mT was detected in this g =
5 (4.9) signal. The shift to g = 5 (4.9) was related
to the distortion of the manganese cluster, derived from the modification
of the chemical bond or the crystalline field of the Mn4(III) in the
manganese cluster. Based on the EPR analysis of the g = 5 (4.9) spin state, another molecular structure of the S2 state, a “distant Mn” structure, was discussed as
an intermediate state between the S2 and S3 states.
Fuligocandin B (2) is a novel natural product that can overcome TRAIL resistance. We synthesized enatiomerically pure fuligocandin B (2) and its derivative 5′‐I fuligocandin B (4), and found that the latter had an improved biological activity against the human gastric cancer cell line, AGS. We attached a biotin linker and photoactivatable aryl diazirine group to 5′‐I fuligocandin B (4), and employed a pull‐down assay to identify valosin‐containing protein (VCP/p97), an AAA ATPase, as a 5′‐I fuligocandin B (4) target protein. Knock‐down of VCP by siRNA enhanced sensitivity to TRAIL in AGS cells. In addition, 4 enhanced CHOP and DR5 protein expression, and overall intracellular levels of ubiquitinated protein. These data suggest that endoplasmic reticulum stress caused through VCP inhibition by 4 increases CHOP‐mediated DR5 up‐regulation, which enhances TRAIL‐induced cell death in AGS cells. To the best of our knowledge, this is the first example to show a relationship between VCP and TRAIL‐resistance‐overcoming activity in cancer cells.
The
high-spin S2 state was investigated with photosystem
II (PSII) from spinach, Thermosynechococcus vulcanus, and Cyanidioschyzon merolae. In extrinsic protein-depleted
PSII, high-spin electron paramagnetic resonance (EPR) signals were
not detected in either species, whereas all species showed g ∼ 5 signals in the presence of a high concentration
of Ca2+ instead of the multiline signal. In the intact
and PsbP/Q-depleted PSII from spinach, the g = 4.1
EPR signal was detected. These results show that formation of the
high-spin S2 state of the manganese cluster is regulated
by the extrinsic proteins through a charge located near the Mn4 atom
in the Mn4CaO5 cluster but is independent of
the intrinsic proteins. The shift to the g ∼
5 state is caused by tilting of the z-axis in the
Mn4 coordinates through hydrogen bonds or external divalent cations.
The structural modification may allow insertion of an oxygen atom
during the S2-to-S3 transition.
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