Mass-dependent bond vibrational dynamics influence catalysis by HIV-1 protease

D. Randal Kipp, Rafael G. Silva, Vern L. Schramm

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Protein motions that occur on the microsecond to millisecond time scale have been linked to enzymatic rates observed for catalytic turnovers, but not to transition-state barrier crossing. It has been hypothesized that enzyme motions on the femtosecond time scale of bond vibrations play a role in transition state formation. Here, we perturb femtosecond motion by substituting all nonexchangeable carbon, nitrogen, and hydrogen atoms with 13C, 15N, and 2H and observe the catalytic effects in HIV-1 protease. According to the Born-Oppenheimer approximation, isotopic substitution alters vibrational frequency with unchanged electrostatic properties. With the use of a fluorescent peptide to report on multiple steps in the reaction, we observe significantly reduced rates in the heavy enzyme relative to the light enzyme. A possible interpretation of our results is that there exists a dynamic link between mass-dependent bond vibrations of the enzyme and events in the reaction coordinate.

Original languageEnglish (US)
Pages (from-to)19358-19361
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number48
DOIs
StatePublished - Dec 7 2011

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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