Intrinsic Domain and Loop Dynamics Commensurate with Catalytic Turnover in an Induced-Fit Enzyme

Omar Davulcu, Peter F. Flynn, Michael S. Chapman, Jack J. Skalicky

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Arginine kinase catalyzes reversible phosphoryl transfer between ATP and arginine, buffering cellular ATP concentrations. Structures of substrate-free and -bound enzyme have highlighted a range of conformational changes thought to occur during the catalytic cycle. Here, NMR is used to characterize the intrinsic backbone dynamics over multiple timescales. Relaxation dispersion indicates rigid-body motion of the N-terminal domain and flexible dynamics in the I182-G209 loop, both at millisecond rates commensurate with kcat, implying that either might be rate limiting upon catalysis. Lipari-Szabo analysis indicates backbone flexibility on the nanosecond timescale in the V308-V322 loop, while the rest of the enzyme is more rigid in this timescale. Thus, intrinsic dynamics are most prominent in regions that have been independently implicated in conformational changes. Substrate-free enzyme may sample an ensemble of different conformations, of which a subset is selected upon substrate binding, with critical active site residues appropriately configured for binding and catalysis.

Original languageEnglish (US)
Pages (from-to)1356-1367
Number of pages12
Issue number10
StatePublished - Oct 14 2009
Externally publishedYes



ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Intrinsic Domain and Loop Dynamics Commensurate with Catalytic Turnover in an Induced-Fit Enzyme'. Together they form a unique fingerprint.

Cite this