Biomedical subjects

Chang No Yoon

Publications and source records attributed to Chang No Yoon.

9 recordsLinked to original sources

PubMed2006

Methodology of the thyroid gland disease decision-making using profiling in steroid hormone pathway.

To find out the genetic factors of outbreak of thyroid gland disease, we developed the thyroid gland decision-making system, which processes the metabolic profile in steroid hormone map using a statistical method. Metabolic profile is a measured data of lots of mixed materials that includes not only known metabolites, but also unknown ones, which is estimated to have an influence on the thyroid gland disease. Therefore, to develop thyroid gland disease decision-making system, analyzing metabolic profile containing multi-materials would be useful for diagnosing thyroid gland disease. Because experimental values used for system construction are area values for the retention time, the observations are preprocessed through variable transition and t-test to use the area values concurrently and the highly correlated materials are estimated by principal component analysis. The thyroid gland decision-making system developed through the logistic regression is an excellent system demonstrating 98.7% accuracy in the classification table.

Algorithms↗

PubMed2006

Design and evolution of new catalytic activity with an existing protein scaffold.

The design of enzymes with new functions and properties has long been a goal in protein engineering. Here, we report a strategy to change the catalytic activity of an existing protein scaffold. This was achieved by simultaneous incorporation and adjustment of functional elements through insertion, deletion, and substitution of several active site loops, followed by point mutations to fine-tune the activity. Using this approach, we were able to introduce beta-lactamase activity into the alphabeta/betaalpha metallohydrolase scaffold of glyoxalase II. The resulting enzyme, evMBL8 (evolved metallo beta-lactamase 8), completely lost its original activity and, instead, catalyzed the hydrolysis of cefotaxime with a (kcat/Km)app of 1.8 x 10(2) (mole/liter)(-1) second(-1), thus increasing resistance to Escherichia coli growth on cefotaxime by a factor of about 100.

Amino Acid Sequence↗

PubMed2005

Identification and functional characterization of novel CYP2J2 variants: G312R variant causes loss of enzyme catalytic activity.

CYP2J2 plays important roles in the metabolism of therapeutic drugs, such as astemizole and ebastine, as well as endogenous fatty acids. This study aimed to identify CYP2J2 genetic variants in Koreans and to characterize their functional consequences. From direct sequencing of the CYP2J2 gene, 12 genetic variations, including the two novel nonsynonymous mutations G312R and P351L, were identified from 93 Korean subjects. The two novel CYP2J2 variants were co-expressed with NADPH-cytochrome P450 reductase in Sf9 cells and their catalytic activities were quantified. The recombinant CYP2J2 G312R variant showed almost complete loss of enzymatic activity, as determined by CYP2J2-catalysed astemizole O-demethylation and ebastine hydroxylation. The CYP2J2 P351L variant showed enzymatic activities that were comparable with the wild-type CYP2J2. The reduced CO spectra of the recombinant CYP2J2 proteins suggested no CO binding to the heme in CYP2J2 G312R. In addition, molecular modelling of the three-dimensional structure consistently predicted that there might be spatial hindrance between heme and the bulky side chain of the R312 residue in CYP2J2 G312R variant. The CYP2J2 G312R variant was not found in 192 Chinese, 99 African-Americans, 100 Caucasians and 159 Vietnamese subjects. Two of the 192 Chinese subjects (0.52%) were heterozygous for CYP2J2 P351L. Twelve CYP2J2 variants, including two novel nonsynonymous variants, were identified in a Korean population. The G312R variant is the first nonfunctional CYP2J2 allele to be identified, and is expected to influence the disposition of its substrate therapeutics, as well as endogenous compounds.

Alleles↗

PubMed2004

Two novel mutations of Wiskott-Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling.

Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326-1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study.

Amino Acid Sequence↗

PubMed2004

Quantitative structure-polarization relationships (QSPR) study of BTEX tracers for the formation of antibody-BTEX-EDF complex.

The multiple linear regression (MLR) analysis and back propagation neural networks (NN) were performed to examine the quantitative structure-polarization relationships (QSPR) for the formation of antibody-BTEX-EDF complex. Five descriptors out of 18 ones were selected for both MLR and NN, respectively, and the selected descriptors in MLR were the same as those in NN. These descriptors were the number of atoms, which can form hydrogen bonds (HA), connolly surface area (Area), the highest occupied molecular orbital energy (HOMO), partial charge of C3 carbon atom (C3), and HOMO pi coefficient of C2 carbon atom (P2). The fact that the descriptors in MLR are identical to those in NN suggests that these descriptors have good linear relationships and play a significant role in the formation of antibody-tracer complex.

Antibodies↗

PubMed2003

An investigation of phosphopeptide binding to SH2 domain.

A comparative molecular field analysis (CoMFA) was carried out to investigate quantitative structure-activity relationships for SH2-binding phosphopeptides. Two alignment rules were applied in our CoMFA model. The phosphopeptide backbone atoms were used for superposition in alignment I and the backbone atoms of peptide-binding residues of SH2-phosphopeptide complexes were used in alignment II to consider the position of phosphopeptides in SH2-binding sites. The higher correlation and predictivity in alignment II (r(2) value of 0.961 and cross-validated r(2) value of 0.682) suggest that the consideration of peptide-binding position at the binding sites gives rise to better results when the ligand-receptor complex structure is considered. In addition, CoMFA contour and electrostatic maps were well accorded with the experimental results in which the replacement of N-terminal residues with an acetyl group reduced the binding affinity. Therefore, the modification of molecular size and charge of phosphopeptides can be carried out based on these contour maps in order to increase binding affinities.

Amino Acid Sequence↗

PubMed2002

Attack vulnerability of complex networks.

We study the response of complex networks subject to attacks on vertices and edges. Several existing complex network models as well as real-world networks of scientific collaborations and Internet traffic are numerically investigated, and the network performance is quantitatively measured by the average inverse geodesic length and the size of the largest connected subgraph. For each case of attacks on vertices and edges, four different attacking strategies are used: removals by the descending order of the degree and the betweenness centrality, calculated for either the initial network or the current network during the removal procedure. It is found that the removals by the recalculated degrees and betweenness centralities are often more harmful than the attack strategies based on the initial network, suggesting that the network structure changes as important vertices or edges are removed. Furthermore, the correlation between the betweenness centrality and the degree in complex networks is studied.

Journal Article↗

PubMed2002

Path finding strategies in scale-free networks.

We numerically investigate the scale-free network model of Barabási and Albert [A. L. Barabási and R. Albert, Science 286, 509 (1999)] through the use of various path finding strategies. In real networks, global network information is not accessible to each vertex, and the actual path connecting two vertices can sometimes be much longer than the shortest one. A generalized diameter depending on the actual path finding strategy is introduced, and a simple strategy, which utilizes only local information on the connectivity, is suggested and shown to yield small-world behavior: the diameter D of the network increases logarithmically with the network size N, the same as is found with global strategy. If paths are sought at random, D is equivalent to N(0.5) is found.

Journal Article↗

PubMedDate not supplied

QSAR analysis of SH2-binding phosphopeptides: using interaction energies and cross-correlation coefficients.

Quantitative structure-activity relationships (QSAR) analyses were carried out on the SH2-phosphopeptide complexes using multiple linear regressions. The residue-residue interaction energies and cross-correlation coefficients were used as descriptors. Since the number of descriptors was very large (602 for interaction energies and 951 for cross-correlation coefficients), the stepwise addition method was applied for the multiple linear regressions. The residue-residue interaction energies were good descriptors for structure-activity relationships. The high r(2) regression models were achieved by using interaction energy. In addition, the concerted atomic motions, which show the dynamic properties during the SH2-phosphopeptide interaction, were used as descriptors. They were identified by the cross-correlation coefficients for atomic displacement. The best regression model, derived by using four cross-correlation coefficients, gave a high r(2) value of 0.925. This suggests that the dynamic properties showing concerted atomic motions can be used as good descriptors in QSAR study.

Amino Acid Sequence↗