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A Physical Model of Mycobacterium tuberculosis MazF‐mt6 Illustrates the Catalytic Residues Needed for 23S rRNA Cleavage via a Proton‐Relay Mechanism
Author(s) -
Dobbins Aaron,
Guzman Karen,
Herm Cayla,
Phillips Evan,
Russell KayLee
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.493.3
Subject(s) - endoribonuclease , 23s ribosomal rna , cleavage (geology) , antitoxin , chemistry , rna , ribosomal rna , biophysics , stereochemistry , biochemistry , biology , ribosome , rnase p , toxin , paleontology , fracture (geology) , gene
Toxin‐antitoxin systems, which are commonly found in prokaryotes, regulate cell growth in response to environmental stressors. When the labile antitoxin is degraded, the toxin is released to exert its inhibitory effects. The Mycobacterium tuberculosis toxin, MazF‐mt6, is a small globular protein composed of two β‐sheets and three α‐helices. This particular protein regulates growth by cleaving the 23S rRNA at helix 70 on the large 50S ribosomal subunit, thus inhibiting translation. The 3D structure of MazF‐mt6 was recently solved by the lab of Dr. Christine Dunham. Their work demonstrated that Asp‐10, Arg‐13, and Thr‐36 are critical residues needed for cleavage within the sequence 5′ UU↓CCU 3′ located at positions 1939 to 1943. These catalytic residues perform endoribonuclease cleavage through a proton‐relay mechanism, where threonine stabilizes the transition state. Lending support to the location of the active site, a negatively charged sulfate ion, which can mimic the negatively charged phosphate backbone of RNA, is found bound adjacent to the residues that appear to participate in the cleavage reaction. We have designed a physical model to illustrate the 3 catalytic residues of the active site, as well as the bound sulfate ion. As is true of any model, physical and computer models provide a means of visualizing protein structure that is useful both as an aid to hypothesis generation and as an instructional tool. Support or Funding Information Campbell University Department of Biological SciencesCBM: NSF‐IUSE #1725940 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .