한국산학기술학회:학술대회논문집 (Proceedings of the KAIS Fall Conference)
- 한국산학기술학회 2012년도 춘계학술논문집 1부
- /
- Pages.182-186
- /
- 2012
사람 티로시나제의 3차원 구조 상동 모델링
Comparative modeling of human tyrosinase - An important target for developing skin whitening agents
- Choi, Jong-Keun (Center for Nutraceutical & Pharmaceutical Materials, Myongji University) ;
- Suh, Joo-Won (Center for Nutraceutical & Pharmaceutical Materials, Myongji University)
- 발행 : 2012.05.25
초록
human tyrosinase (hTyr) catalyzes first and the rate limiting step in the synthesis of polymerized pigment, melanin which determines skin, hair and eye colors. Mutation of hTyr often brings about decrease of melanin production and further albinism. Meanwhile, a number of cosmetic companies providing skincare products for woman in Asia-Pacific region have tried to develop inhibitors to bright skin color for several decades. In this study, we built a 3D structure by comparative modeling technique based on the crystal structure of tyrosinase from bacillus megaterium as a template to serve structural information of hTyr. According to our model and sequence analysis of type 3 copper protein family proteins, two copper atoms of active site located deep inside are coordinated with six strictly conserved histidine residues coming from four-helix-bundle. Cavity which accommodates substrates was like funnel shape of which entrance was wide and expose to solvent. In addition, protein-substrate and protein-inhibitor complex were modeled with the guide of van der waals surface generated by in house software. Our model suggested that only phenol group or its analogs can fill the binding site near nuclear copper center because inside of binding site has narrow shape relatively. In conclusion, the results of this study may provide helpful information for designing and screening new anti-melanogensis agents.
키워드