近日，上海科技大學免疫化學研究所饒子和/楊海濤團隊解析的2019-新型冠狀病毒3CL水解酶（Mpro）的高解析度晶體結構被PDB蛋白質結構資料庫（Protein Data Bank, PDB）選為2020年2月的本月明星分子（February Molecule of the Month）。PDB還撰文指出，作為目前唯一已解析的2019-新型冠狀病毒的蛋白結構，3CL水解酶（Mpro）結構數據的及時公開，將推進對於新型冠狀病毒這一新發現人類病原體的研究及藥物發現，有助於科研人員及臨床醫生應對新型冠狀病毒的疫情。
2019-新型冠狀病毒3CL水解酶 Mpro晶體結構
PDB 結構之星（2019-新型冠狀病毒3CL水解酶 Mpro晶體結構）
在新型冠狀病毒肺炎疫情出現後，饒子和/楊海濤團隊迅速響應，利用多年SARS研究積累的經驗，僅用一周時間就解析了2019-新型冠狀病毒的最關鍵蛋白之一——3CL水解酶的高解析度晶體結構（數據收集在上海光源完成）。2020年1月26日，團隊預先公布了2019-新型冠狀病毒3CL水解酶（Mpro）的高解析度晶體結構，晶體結構坐標可到PDB蛋白質結構資料庫下載（PDB ID: 6LU7）。
為方便更多的科技工作者第一時間開發以該水解酶為靶點的抗2019-新型冠狀病毒藥物，在PDB可下載前，饒子和/楊海濤課題組就已為國內外300多家高校、研究機構及公司的實驗室直接提供了結構數據。
註：PDB蛋白質資料庫是一個開放的生物大分子 （蛋白質、DNA和RNA）結構的資料庫，是結構生物學研究的重要資源。作為生物學及醫學中第一個開放的數字數據資源，PDB致力於實現科學和生物醫學研究與教育的突破，積極拓展基礎生物學、生物醫學和生物技術的前沿，在全球範圍內推動了人類和動物的健康和疾病，植物、食品和能源生產，及其他全球繁榮和可持續性相關領域的高質量研究。
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文章來源：PDB 2020/02/04
New Coronavirus Protease Structure Available
PDB data provide a starting point for structure-guided drug discovery
A high-resolution crystal structure of 2019-nCoV coronavirus 3CL hydrolase(Mpro)has been determined by Zihe Rao and Haitao Yang's research team at ShanghaiTech University. Rapid public release of this structure of the main protease of the virus(PDB 6lu7)will enable research on this newly-recognized human pathogen.
Recent emergence of the 2019-nCoV coronavirus has resulted in a WHO-declared public health emergency of international concern. Research efforts around the world are working towards establishing a greater understanding of this particular virus and developing treatments and vaccines to prevent further spread.
https://doi.org/10.2210/pdb6lu7/pdb
While PDB entry 6lu7 is currently the only public-domain 3D structure from this specific coronavirus, the PDB contains structures of the corresponding enzyme from other coronaviruses. The 2003 outbreak of the closely-related Severe Acute Respiratory Syndrome-related coronavirus(SARS)led to the first 3D structures, and today there are more than 200 PDB structures of SARS proteins. Structural information from these related proteins could be vital in furthering our understanding of coronaviruses and in discovery and development of new treatments and vaccines to contain the current outbreak. The coronavirus 3CL hydrolase(Mpro)enzyme, also known as the main protease, is essential for proteolytic maturation of the virus. It is thought to be a promising target for discovery of small-molecule drugs that would inhibit cleavage of the viral polyprotein and prevent spread of the infection. Comparison of the protein sequence of the 2019-nCoV coronavirus 3CL hydrolase(Mpro)against the PDB archive identified 95 PDB proteins with at least 90% sequence identity. Furthermore, these related protein structures contain approximately 30 distinct small molecule inhibitors, which could guide discovery of new drugs. Of particular significance for drug discovery is the very high amino acid sequence identity(96%)between the 2019-nCoV coronavirus 3CL hydrolase(Mpro)and the SARS virus main protease(PDB 1q2w). Summary data about these closely-related PDB structures are available to help researchers more easily find this information. In addition, the PDB houses 3D structure data for more than 20 unique SARS proteins represented in more than 200 PDB structures, including a second viral protease, the RNA polymerase, the viral spike protein, a viral RNA, and other proteins.
Public release of the 2019-nCoV coronavirus 3CL hydrolase(Mpro), at a time when this information can prove most vital and valuable, highlights the importance of open and timely availability of scientific data. The wwPDB strives to ensure that 3D biological structure data remain freely accessible for all, while maintaining as comprehensive and accurate an archive as possible. We hope that this new structure, and those from related viruses, will help researchers and clinicians address the 2019-nCoV coronavirus global public health emergency.
文章連結：
https://www.rcsb.org/news?year=2020&article=5e39e03fa5007a04a313edc3