Compound Molecular Logic in Accessing the Active Site of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B.

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.

• Publication year

  2018

• Venue

  Journal of the American Chemical Society

• Publication date

  2018-10-10

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/jacs.8b08070PMID 30301350
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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