Browsing by Author "Morrell, Thomas E."

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Compound Molecular Logic in Accessing the Active Site of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B
(2018-11-07)
Morrell, Thomas E.
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Rafalska-Metcalf, Ilona U.
;
Yang, Haw
;
Chu, Jhih-Wei
;
生物資訊及系統生物研究所
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.
Coupling between Protein Conformation and Local Unfolding Highlights the Role of Disorder in Protein Function and Suggests a New Target for Tuberculosis Treatment
(2014-01-28)
Morrell, Thomas E.
;
Rafalska-Metcalf, Ilona U.
;
Chu, Jhih-Wei
;
Yang, Haw
;
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