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Conformational coupling, bridge helix dynamics and active site dehydration in catalysis by RNA polymerase

  1. Author:
    Seibold, S. A.
    Singh, B. N.
    Zhang, C. F.
    Kireeva, M.
    Domecq, C.
    Bouchard, A.
    Nazione, A. M.
    Feig, M.
    Cukier, R. I.
    Coulombe, B.
    Kashlev, M.
    Hampsey, M.
    Burton, Z. F.

  2. Author Address

    [Seibold, Steve A.; Zhang, Chunfen; Nazione, Anthony M.; Feig, Michael; Burton, Zachary F.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Seibold, Steve A.; Feig, Michael; Cukier, Robert I.] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. [Singh, Badri Nath; Hampsey, Michael] Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA. [Kireeva, Maria; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. [Domecq, Celine; Bouchard, Annie; Coulombe, Benoit] Inst Rech Clin Montreal, Gene Transcript & Prote Lab, Montreal, PQ H2W 1R7, Canada.;Burton, ZF, Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA.;burton@cns.msu.edu
    1. Year: 2010
    2. Date: Aug
  2. Journal: Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms
    1. 1799
    2. 8
    3. Pages: 575-587
  4. Type of Article: Article
  5. ISSN: 1874-9399
  1. Abstract:

    Molecular dynamics simulation of Thermus thermophilus (Tt) RNA polymerase (RNAP) in a catalytic conformation demonstrates that the active site dNMP-NTP base pair must be substantially dehydrated to support full active site closing and optimum conditions for phosphodiester bond synthesis. In silico mutant beta R428A RNAP, which was designed based on substitutions at the homologous position (Rpb2 R512) of Saccharomyces cerevisiae (Sc) RNAP II, was used as a reference structure to compare to Tt RNAP in simulations. Long range conformational coupling linking a dynamic segment of the bridge alpha-helix, the extended fork loop, the active site, and the trigger loop-trigger helix is apparent and adversely affected in 13 R428A RNAP. Furthermore, bridge helix bending is detected in the catalytic structure, indicating that bridge helix dynamics may regulate phosphodiester bond synthesis as well as translocation. An active site "latch" assembly that includes a key trigger helix residue Tt beta' H1242 and highly conserved active site residues 13 E445 and R557 appears to help regulate active site hydration/dehydration. The potential relevance of these observations in understanding RNAP and DNAP induced fit and fidelity is discussed. (C) 2010 Elsevier B.V. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.bbagrm.2010.05.002
  3. View record in Web of Science®
  4. WOS: 000281932600007

Library Notes

  1. Fiscal Year: FY2009-2010
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