• 한국자기공명학회논문지
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• 제23권1호
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• pp.26-32
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• 2019

${\alpha}B$-crystallin (${\alpha}BC$) is a member of a small heat-shock protein (sHSP) superfamily and plays a predominant role in cellular protein homeostasis network by rescuing misfolded proteins from irreversible aggregation. ${\alpha}BC$ assembles into dynamic and polydisperse high molecular weight complexes containing 12 to 48 monomers; this variable stereochemistry of ${\alpha}BC$ has been linked to quaternary subunit exchange and its chaperone activity. The chaperone activity of ${\alpha}BC$ poses great potential as therapeutic agents for various neurodegenerative diseases. In this mini-review, we briefly outline the recent advancement in structural characterization of ${\alpha}BCs$ and its potential role to inhibit protein misfolding and aggregation in various human diseases. In particular, nuclear magnetic resonance (NMR) spectroscopy and its complimentary techniques have contributed much to elucidate highly-dynamic nature of ${\alpha}BCs$, among which notable advancements are discussed in detail. We highlight the importance of resolving the structural details of various ${\alpha}BC$ oligomers, their quaternary dynamics, and structural heterogeneity.

• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.469-476
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• 2012

2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is an environmental toxicant with a polyhalogenated aromatic hydrocarbon structure and is one of the most toxic man-made chemicals. Exposure to 2,3,7,8-TCDD induces reproductive toxicity, immunotoxicity, and hepatotoxicity. In this study, we evaluated how 2,3,7,8-TCDD-induced hepatotoxicity affect the expression of heat shock proteins and antioxidant enzymes using the real-time polymerase chain reaction (PCR) in rat. 2,3,7,8-TCDD increased heat shock protein (Hsp27, ${\alpha}$-B-crystallin, Mortalin, Hsp105, and Hsp90s) and antioxidant enzymes (SOD-3, GST and catalase) expression after a 1 day exposure in livers of rats, whereas heat shock protein (${\alpha}$-B-crystallin, Hsp90, and GRP78) and antioxidant enzymes (SOD-1, SOD-3, catalase, GST, and GPXs) expression decreased on day 2 and then slowly recovered back to control levels on day 8. These results suggest that heat shock proteins and antioxidant enzymes were induced as protective mechanisms against 2,3,7,8-TCDD induced hepatotoxicity, and that prolonged exposure depressed their levels, which recovered to control levels due to reduced 2,3,7,8-TCDD induced hepatotoxicity.

• Molecules and Cells
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• 제41권4호
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• pp.331-341
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• 2018

L-pipecolic acid is a non-protein amino acid commonly found in plants, animals, and microorganisms. It is a well-known precursor to numerous microbial secondary metabolites and pharmaceuticals, including anticancer agents, immunosuppressants, and several antibiotics. Lysine cyclodeaminase (LCD) catalyzes ${\beta}$-deamination of L-lysine into L-pipecolic acid using ${\beta}$-nicotinamide adenine dinucleotide as a cofactor. Expression of a human homolog of LCD, ${\mu}$-crystallin, is elevated in prostate cancer patients. To understand the structural features and catalytic mechanisms of LCD, we determined the crystal structures of Streptomyces pristinaespiralis LCD (SpLCD) in (i) a binary complex with $NAD^+$, (ii) a ternary complex with $NAD^+$ and L-pipecolic acid, (iii) a ternary complex with $NAD^+$ and L-proline, and (iv) a ternary complex with $NAD^+$ and L-2,4-diamino butyric acid. The overall structure of SpLCD was similar to that of ornithine cyclodeaminase from Pseudomonas putida. In addition, SpLCD recognized L-lysine, L-ornithine, and L-2,4-diamino butyric acid despite differences in the active site, including differences in hydrogen bonding by Asp236, which corresponds with Asp228 from Pseudomonas putida ornithine cyclodeaminase. The substrate binding pocket of SpLCD allowed substrates smaller than lysine to bind, thus enabling binding to ornithine and L-2,4-diamino butyric acid. Our structural and biochemical data facilitate a detailed understanding of substrate and product recognition, thus providing evidence for a reaction mechanism for SpLCD. The proposed mechanism is unusual in that $NAD^+$ is initially converted into NADH and then reverted back into $NAD^+$ at a late stage of the reaction.

• 공업화학
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• 제19권5호
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• pp.457-465
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• 2008

인간의 질병을 치료하기 위한 여러 가지 의료 시스템의 개발이 생명공학의 발전과 함께 많은 연구가 이루어지고 있다. 또한 약물이나 유전자와 같은 생리활성물질을 체내에 안전하게 전달할 수 있는 시스템의 개발과 함께 이루어지고 있다. 이러한 시스템에 있어서 가장 중요한 것은 생체적합성 및 생체분해성 그리고 무독성의 특성을 가진 생체의료용 고분자를 개발하는 것이다. 천연고분자물질인 키토산은 좋은 생체적합성과 생체활성의 특성을 가지고 있어서 생체의료용 재료로 심도 있게 고려되어지고 있다. 키토산의 물성은 키틴의 결정성 구조에 따라 다르게 설명되므로 키틴의 구조적 분석에 대한 연구가 생체재료로써의 응용을 위해서 선행되어야 한다. 이러한 관점에서 본 총설에서는 키틴의 결정성 구조 분석, 키토산의 일반적인 물성 그리고 생체의료용 재료로써 저분자량 수용성 키토산의 가능성을 소개하였다. 또한 다양한 기능성기를 이용한 저분자량 수용성 키토산의 화학적인 개질을 약물전달체로써의 가능성을 강조하고 생체이용율의 향상을 위해 수행하였다.