非典型肺炎3CL蛋白酶C145A突變蛋白受質結合態的結晶結構：提供以結構基礎藥物設計的線索

Crystal structure of SARS 3CL mutant C145A in a product-bound state: implication for the design of structure-based inhibitors

張凱棣(KAI-TI CHANG)

指導教授 ： 王惠鈞

國立臺灣大學/生命科學院/生化科學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.01209

摘要

一種新型的冠狀病毒(SARS-CoV)是造成嚴重急性呼吸道症候群
爆發的原因。這個冠狀病毒利用SARS 3C-like proteinase 做大範圍的
酵素分解反應來產生複製和轉譯所需要的酵素。因為這個原因SARS
3C-like proteinase 就成為藥物設計的主要目標。把在SARS 3C-like
proteinase 中，參與催化作用的一個殘基，位於第145 的半氨胱酸
cysteine)，突變成丙胺酸(Alanine)。這個突變的酵素依序被大量表
現、純化和結晶。得到一個單斜晶系、空間群為C2 和解析度2.5 Å
的晶體。每個不對稱單元(asymmetric unit)含有一個二聚體。由結構知
道活性區域被屬於另一個不稱單元的單體所鑲嵌。這個研究提供一些
資訊來了解基質和酵素結合，能夠幫助針對嚴重呼吸道症候群或是其
他相關冠狀病毒的藥物設計。

關鍵字

結晶 ； 非典型肺炎 ； 冠狀病毒 ； 結構

並列摘要

A newly identified severe acute respiratory syndrome coronavirus
(SARS-CoV) is the etiological agent responsible for the outbreak of
severe acute respiratory syndrome (SARS). The 3C-like proteinase (also
called main proteinase) is a key enzyme for mediating viral replication
and transcription through extensive proteolytic processing and an
essential target for drug development. One of the catalytic residues of
SARS 3C-like protease, Cys145, was replaced with Ala and the C145A
mutant was over-expressed, purified and crystallized. The plate-like
crystal diffracts to 2.5Å and belongs to C2 space group. There is one
dimer in an asymmetric unit. The structure revealed that the active site
region is penetrated by another monomer which belongs to another
asymmetric unit. This study provides a basic understanding of the
substrate binding, which is helpful for the design of structure-based
inhibitors SARS and related coronaviruses.

並列關鍵字

3C-like proteinase ； main proteinase ； crystal structure ； severe acute repiratory syndrom ； coronavirus ； SARS ； 3CL

參考文獻

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