標題: Compound Molecular Logic in Accessing the Active Site of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B
作者: Morrell, Thomas E.
Rafalska-Metcalf, Ilona U.
Yang, Haw
Chu, Jhih-Wei
生物資訊及系統生物研究所
分子醫學與生物工程研究所
Institude of Bioinformatics and Systems Biology
Institute of Molecular Medicine and Bioengineering
公開日期: 7-Nov-2018
摘要: Protein tyrosine phosphatase B (PtpB) from Mycobacterium tuberculosis (Mtb) extends the bacteria's survival in hosts and hence is a potential target for Mtb-specific drugs. To study how Mtb-specific sequence insertions in PtpB may regulate access to its active site through large-amplitude conformational changes, we performed free-energy calculations using an all-atom explicit solvent model. Corroborated by biochemical assays, the results show that PtpB's active site is controlled via an "either/or" compound conformational gating mechanism, an unexpected discovery that Mtb has evolved to bestow a single enzyme with such intricate logical operations. In addition to providing unprecedented insights for its active-site surroundings, the findings also suggest new ways of inactivating PtpB.
URI: http://dx.doi.org/10.1021/jacs.8b08070
http://hdl.handle.net/11536/148443
ISSN: 0002-7863
DOI: 10.1021/jacs.8b08070
期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume: 140
起始頁: 14747
結束頁: 14752
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