Molecular, Evolutionary, and Structural Analysis of the Terminal Protein Domain of Hepatitis B Virus Polymerase, a Potential Drug Target
Timothy S Buhlig 1 , Anastasia F Bowersox 2 , Daniel L Braun 2 , Desiree N Owsley 1 , Kortney D James 1 , Alfredo J Aranda 1 , Connor D Kendrick 1 , Nicole A Skalka 1 , Daniel N Clark 1
Affiliations
Affiliations
1
Microbiology Department, Weber State University, 1415 Edvalson St., Ogden, UT 84408, USA.
2
Biology Department, Lebanon Valley College, 101 N. College Ave., Annville, PA 17003, USA.
PMID: 32455999 DOI: 10.3390/v12050570
Free article
Abstract
Approximately 250 million people are living with chronic hepatitis B virus (HBV) infections, which claim nearly a million lives annually. The target of all current HBV drug therapies (except interferon) is the viral polymerase; specifically, the reverse transcriptase domain. Although no high-resolution structure exists for the HBV polymerase, several recent advances have helped to map its functions to specific domains. The terminal protein (TP) domain, unique to hepadnaviruses such as HBV, has been implicated in the binding and packaging of the viral RNA, as well as the initial priming of and downstream synthesis of viral DNA-all of which make the TP domain an attractive novel drug target. This review encompasses three types of analysis: sequence conservation analysis, secondary structure prediction, and the results from mutational studies. It is concluded that the TP domain of HBV polymerase is comprised of seven subdomains (three unstructured loops and four helical regions) and that all three loop subdomains and Helix 5 are the major determinants of HBV function within the TP domain. Further studies, such as modeling inhibitors of these critical TP subdomains, will advance the TP domain of HBV polymerase as a therapeutic drug target in the progression towards a cure.
Keywords: hepatitis B virus; protein priming; terminal protein. 作者: StephenW 时间: 2020-5-29 13:35
乙型肝炎病毒聚合酶（潜在的药物靶标）末端蛋白质域的分子，进化和结构分析
Timothy S Buhlig 1，Anastasia F Bowersox 2，Daniel L Braun 2，Desiree N Owsley 1，Kortney D James 1，Alfredo J Aranda 1，Connor D Kendrick 1，Nicole A Skalka 1，Daniel N Clark 1
隶属关系
隶属关系
1个
韦伯州立大学微生物系，美国奥格登市爱德华森街1415号，犹他州84408，美国。
2
黎巴嫩谷学院生物系，美国宾夕法尼亚州安维尔市N. College Ave. 101号，宾夕法尼亚州17003。