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Localized network centrality and essentiality in the yeast–protein interaction network
Park, Keunwan,Kim, Dongsup WILEY-VCH Verlag 2009 Proteomics Vol.9 No.22
<P>It has been suggested that a close relationship exists between gene essentiality and network centrality in protein–protein interaction networks. However, recent studies have reported somewhat conflicting results on this relationship. In this study, we investigated whether essential proteins could be inferred from network centrality alone. In addition, we determined which centrality measures describe the essentiality well. For this analysis, we devised new local centrality measures based on several well-known centrality measures to more precisely describe the connection between network topology and essentiality. We examined two recent yeast protein–protein interaction networks using 40 different centrality measures. We discovered a close relationship between the path-based localized information centrality and gene essentiality, which suggested underlying topological features that represent essentiality. We propose that two important features of the localized information centrality (proper representation of environmental complexity and the consideration of local sub-networks) are the key factors that reveal essentiality. In addition, a random forest classifier showed reasonable performance at classifying essential proteins. Finally, the results of clustering analysis using centrality measures indicate that some network clusters are closely related with both particular biological processes and essentiality, suggesting that functionally related proteins tend to share similar network properties.</P>
Color-Tuning Mechanism of the Lit Form of Orange Carotenoid Protein
Jiyong Park,Man-Hyuk Han,Hee Wook Yang,Jungmin Yoon,Yvette Villafani,Ji-Young Song,Cheol Ho Pan,Keunwan Park,Youngmoon Cho,송지준,Seung Joong Kim,박연일 한국분자세포생물학회 2023 Molecules and cells Vol.46 No.8
Orange carotenoid protein (OCP) of photosynthetic cyanobacteria binds to ketocarotenoids noncovalently and absorbs excess light to protect the host organism from light-induced oxidative damage. Herein, we found that mutating valine 40 in the α3 helix of Gloeocapsa sp. PCC 7513 (GlOCP1) resulted in blue- or red-shifts of 6-20 nm in the absorption maxima of the lit forms. We analyzed the origins of absorption maxima shifts by integrating X-ray crystallography, homology modeling, molecular dynamics simulations, and hybrid quantum mechanics/molecular mechanics calculations. Our analysis suggested that the single residue mutations alter the polar environment surrounding the bound canthaxanthin, thereby modulating the degree of charge transfer in the photoexcited state of the chromophore. Our integrated investigations reveal the mechanism of color adaptation specific to OCPs and suggest a design principle for color-specific photoswitches.
Lee, Byung-Chul,Park, Keunwan,Kim, Dongsup Wiley Subscription Services, Inc., A Wiley Company 2008 Proteins Vol.72 No.3
<P>It is a common belief that some residues of a protein are more important than others. In some cases, point mutations of some residues make butterfly effect on the protein structure and function, but in other cases they do not. In addition, the residues important for the protein function tend to be not only conserved but also coevolved with other interacting residues in a protein. Motivated by these observations, the authors propose that there is a network composed of the residues, the residue–residue coevolution network (RRCN), where nodes are residues and links are set when the coevolutionary interaction strengths between residues are sufficiently large. The authors build the RRCN for the 44 diverse protein families. The interaction strengths are calculated by using McBASC algorithm. After constructing the RRCN, the authors identify residues that have high degree of connectivity (hub nodes), and residues that play a central role in network flow of information (C<SUP>I</SUP> nodes). The authors show that these residues are likely to be functionally important residues. Moreover, the C<SUP>I</SUP> nodes appear to be more relevant to the function than the hub nodes. Unlike other similar methods, the method described in this study is solely based on sequences. Therefore, the method can be applied to the function annotation of a wider range of proteins. Proteins 2008. © 2008 Wiley-Liss, Inc.</P>
Neuroprotective Mechanism of Corydaline in Glutamate-Induced Neurotoxicity in HT22 Cells
Baskar Selvaraj,Dae Won Kim,Ki Yeon Yoo,Keunwan Park,Thi Thu Thuy Tran,Jae Wook Lee,Heesu Lee 대한구강생물학회 2024 International Journal of Oral Biology Vol.49 No.1
Glutamate-mediated oxidative stress causes neuronal cell death by increasing intracellular Ca 2+ uptake, reactive oxidative species (ROS) generation, mitogen-activated protein kinase (MAPK) activation, and translocation of apoptosis-inducing factor (AIF) to the nucleus. In the current study, we demonstrated that corydaline exerts potent neuroprotective effects against glutamate-induced neurotoxicity. Treatment with 5 mmol/L glutamate increased cellular Ca 2+ influx, ROS generation, MAPK activation, and AIF translocation. In contrast, corydaline treatment decreased cellular Ca 2+ influx and ROS generation. Western blot analysis revealed that glutamate-mediated MAPK activation was attenuated by corydaline treatment. We further demonstrated that corydaline treatment inhibited the glutamate-mediated translocation of AIF to the nucleus. We propose that corydaline is a promising lead structure for the development of safe and effective neuroprotectants.
Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase Iα and δ
Lee, Jae Wook,Hirota, Tsuyoshi,Ono, Daisuke,Honma, Sato,Honma, Ken-ichi,Park, Keunwan,Kay, Steve A. American Chemical Society 2019 Journal of medicinal chemistry Vol.62 No.4
<P>Circadian rhythms are controlled by transcriptional feedback loops of clock genes and proteins. The stability of clock proteins is regulated by post-translational modification, such as phosphorylation by kinases. In particular, casein kinase I (CKI) phosphorylates the PER protein to regulate proteasomal degradation and nuclear localization. Therefore, CKI inhibition can modulate mammalian circadian rhythms. In the present study, we have developed novel CKIα and CKIδ dual inhibitors by extensive structural modification of N9 and C2 position of longdaysin. We identified NCC007 that showed stronger period effects (0.32 μM for 5 h period lengthening) in a cell-based circadian assay. The following in vitro kinase assay showed that NCC007 inhibited CKIα and CKIδ with an IC<SUB>50</SUB> of 1.8 and 3.6 μM. We further demonstrated that NCC007 lengthened the period of mouse behavioral rhythms in vivo. Thus, NCC007 is a valuable tool compound to control circadian rhythms through CKI inhibition.</P> [FIG OMISSION]</BR>