Biomedical subjects

Seung-Jun Kim

Publications and source records attributed to Seung-Jun Kim.

5 recordsLinked to original sources

PubMed2004

The intelligent data management system for toxicogenomics.

Toxicogenomics is now emerging as one of the most important genomic application because the toxicity test based on gene expression profiles is expected to be more precise and efficient than current histopathological approaches in a pre-clinical phase. One of the challenging issues in toxicogenomics is the construction of intelligent database management system which can deal with heterogeneous and complex data from many different experimental and information sources. TEST(Toxicogenomics for Efficient Safety Test) database is especially focused on the connectivity of heterogeneous data and the intelligent query system which enable users to obtain relevant useful information from the complex data sets. The database deals with four kinds of information; compound, histopathology, gene expression, and annotation information. Currently, TEST database maintains toxicogenomics information for 16 compounds, 45 microarrays, 190 animal experiments, and customized 4.8 K rat clone set. Our presented system is expected to be a good information source for studying of toxicology mechanism in the genome-wide level and can also be applied to the designing toxicity test chip.

Animals↗

PubMed2004

cDNA microarray gene expression analysis and toxicological phenotype for anticancer drug.

Toxicogenomics, the subdiscipline that merges genomics with toxicology, hold the promise to contributing toward the goal of elucidating mechanism by studying genomic profiling related with various drugs. The application of gene expression profiling technology to examine multiple genes and signaling pathways promises a significant advance in understanding the toxic mechanisms of various drugs and prediction of new drug candidate. Toxicogenomics is emerging field combining genomics and bioinformatics to identify and characterize mechanisms of toxicity of drug and various compounds. The principal hypothesis underlying on this field is that chemical-specific pattern of altered gene expression is related with each chemicals properties, especially toxicological property, and it will be revealed using high-density microarray analysis of sample from exposed organisms. So, in this study we compare the gene expression pattern of two anticancer drugs paclitaxel and orally absorbable paclitaxel, using the cDNA microarray. And from the result of this study, it is possible to provide the new possibility for genome-wide insight into mechanism of their anticancer activity and toxicological phenotype.

Administration, Oral↗

PubMed2003

Origin of the stereospecificity in binding hydroxamates of alpha- and beta-phenylalanine methylamide to thermolysin revealed by the X-ray crystallographic study.

Optically active N-formyl-N-hydroxy-alpha-phenylalanine methylamide (1) and N-formyl-N-hydroxy-beta-phenylalanine methylamide (2) were evaluated as inhibitors for thermolysin (TLN) to find that while the D-form is more potent than its enantiomer in the case of the hydroxamate of alpha-Phe-NHMe, in the inhibition with hydroxamate of beta-Phe-NHMe, the L-isomer (K(i)=1.66+/-0.05 microM) is more effective than its enantiomer. In order to shed light on the stereochemical preference observed in the inhibitions, X-ray crystallographic analyses of the crystalline TLN.D-1 and TLN.L-2 complexes were performed to the resolution of 2.1A. While L-2 binds TLN like substrate does with its benzyl aromatic ring occupying the S(1)' pocket, the electron density in the S(1)' pocket in the complex of TLN.D-1 is weak and could best be accounted for by the methylcarbamoyl moiety. For both inhibitors, the hydroxamate moiety coordinates the active site zinc ion in a bidentate fashion.

Amides↗

PubMed2002

Sulfamide-based inhibitors for carboxypeptidase A. Novel type transition state analogue inhibitors for zinc proteases.

N-Sulfamoylphenylalanine and its derivatives having varied alkyl groups on the terminal amino group were designed rationally as transition state analogue inhibitors for carboxypeptidase A (CPA) and synthesized. In CPA inhibitory assays the parent compound having the (S)-configuration, i.e., (S)-1a, showed potent inhibitory activity with the K(i) value of 0.64 microM. Its enantiomer was shown to be much less potent (K(i) = 470 microM). Introduction of an alkyl group such as methyl or isopropyl group on the terminal amino group of (S)-1a lowered the inhibitory potency drastically. Introduction of a methyl group on the internal amino group of (S)-1a also caused a drastic reduction of the inhibitory activity. The structure of the CPA x(S)-1a complex determined by single-crystal X-ray diffraction reveals that the sulfamoyl moiety interacts with the zinc ion and functional groups at the active site of CPA, which is reminiscent of the postulated stabilization mode of a tetrahedral transition state in the CPA-catalyzed hydrolysis of a peptide substrate. On the basis of the design rationale and the binding mode of (S)-1a to CPA shown by X-ray crystallographic analysis, the present inhibitors are inferred to be a novel type of transition state analogue inhibitor for CPA.

Carboxypeptidases↗

PubMed2002

Novel zinc-binding center and a temperature switch in the Bacillus stearothermophilus L1 lipase.

The bacterial thermoalkalophilic lipases optimally hydrolyze saturated fatty acids at elevated temperatures. They also have significant sequence homology with staphylococcal lipases, and both the thermoalkalophilic and staphylococcal lipases are grouped as the lipase family I.5. We report here the first crystal structure of the lipase family I.5, the structure of a thermoalkalophilic lipase from Bacillus stearothermophilus L1 (L1 lipase) determined at 2.0-A resolution. The structure is in a closed conformation, and the active site is buried under a long lid helix. Unexpectedly, the structure exhibits a zinc-binding site in an extra domain that accounts for the larger molecular size of the family I.5 enzymes in comparison to other microbial lipases. The zinc-coordinated extra domain makes tight interactions with the loop extended from the C terminus of the lid helix, suggesting that the activation of the family I.5 lipases may be regulated by the strength of the interactions. The unusually long lid helix makes strong hydrophobic interactions with its neighbors. The structural information together with previous biochemical observations indicate that the temperature-mediated lid opening is triggered by the thermal dissociation of the hydrophobic interactions.

Amino Acid Sequence↗