Biomedical subjects

Ook Joon Yoo

Publications and source records attributed to Ook Joon Yoo.

4 recordsLinked to original sources

PubMed2003

Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril.

Angiotensin I-converting enzymes (ACEs) are zinc metallopeptidases that cleave carboxy-terminal dipeptides from short peptide hormones. We have determined the crystal structures of AnCE, a Drosophila homolog of ACE, with and without bound inhibitors to 2.4 A resolution. AnCE contains a large internal channel encompassing the entire protein molecule. This substrate-binding channel is composed of two chambers, reminiscent of a peanut shell. The inhibitor and zinc-binding sites are located in the narrow bottleneck connecting the two chambers. The substrate and inhibitor specificity of AnCE appears to be determined by extensive hydrogen-bonding networks and ionic interactions in the active site channel. The catalytically important zinc ion is coordinated by the conserved Glu395 and histidine residues from a HExxH motif.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation.

B-cell activating factor (BAFF) is a key regulator of B-lymphocyte development. Its biological role is mediated by the specific receptors BCMA, TACI and BAFF-R. We have determined the crystal structure of the extracellular domain of BAFF-R bound to BAFF at a resolution of 3.3 A. The cysteine-rich domain (CRD) of the BAFF-R extracellular domain adopts a beta-hairpin structure and binds to the virus-like BAFF cage in a 1:1 molar ratio. The conserved DxL motif of BAFF-R is located on the tip of the beta-turn and is indispensable in the binding of BAFF. The crystal structure shows that a unique dimeric contact occurs between the BAFF-R monomers in the virus-like cage complex. The extracellular domain of TACI contains two CRDs, both of which contain the DxL motif. Modeling of TACI-BAFF complex suggests that both CDRs simultaneously interact with the BAFF dimer in the virus-like cage.

Amino Acid Sequence↗

PubMed2003

Combining multiple microarray studies and modeling interstudy variation.

We have established a method for systematic integration of multiple microarray datasets. The method was applied to two different sets of cancer profiling studies. The change of gene expression in cancer was expressed as 'effect size', a standardized index measuring the magnitude of a treatment or covariate effect. The effect sizes were combined to obtain the estimate of the overall mean. The statistical significance was determined by a permutation test extended to multiple datasets. It was shown that the data integration promotes the discovery of small but consistent expression changes with increased sensitivity and reliability. The effect size methods provided the efficient modeling framework for addressing interstudy variation as well. Based on the result of homogeneity tests, a fixed effects model was adopted for one set of datasets that had been created in controlled experimental conditions. By contrast, a random effects model was shown to be appropriate for the other set of datasets that had been published by independent groups. We also developed an alternative modeling procedure based on a Bayesian approach, which would offer flexibility and robustness compared to the classical procedure.

Algorithms↗

PubMed2002

A large population of small chloroplasts in tobacco leaf cells allows more effective chloroplast movement than a few enlarged chloroplasts.

We generated transgenic tobacco (Nicotiana tabacum cv Xanthi) plants that contained only one to three enlarged chloroplasts per leaf mesophyll cell by introducing NtFtsZ1-2, a cDNA for plastid division. These plants were used to investigate the advantages of having a large population of small chloroplasts rather than a few enlarged chloroplasts in a leaf mesophyll cell. Despite the similarities in photosynthetic components and ultrastructure of photosynthetic machinery between wild-type and transgenic plants, the overall growth of transgenic plants under low- and high-light conditions was retarded. In wild-type plants, the chloroplasts moved toward the face position under low light and toward the profile position under high-light conditions. However, chloroplast rearrangement in transgenic plants in response to light conditions was not evident. In addition, transgenic plant leaves showed greatly diminished changes in leaf transmittance values under both light conditions, indicating that chloroplast rearrangement was severely retarded. Therefore, under low-light conditions the incomplete face position of the enlarged chloroplasts results in decreased absorbance of light energy. This, in turn, reduces plant growth. Under high-light conditions, the amount of absorbed light exceeds the photosynthetic utilization capacity due to the incomplete profile position of the enlarged chloroplasts, resulting in photodamage to the photosynthetic machinery, and decreased growth. The presence of a large number of small and/or rapidly moving chloroplasts in the cells of higher land plants permits more effective chloroplast phototaxis and, hence, allows more efficient utilization of low-incident photon flux densities. The photosynthetic apparatus is, consequently, protected from damage under high-incident photon flux densities.

Biological Transport↗