Jump to main content
Jump to site search

Issue 9, 2012
Previous Article Next Article

Hydrogen-bond stabilization in oxyanion holes: grand jeté to three dimensions

Author affiliations

Abstract

We recently reported crystallographic evidence that the hydrogen bonds which can stabilize oxygen-centered negative charge within enzyme oxyanion holes are rarely found in the place they should be expected on the basis of the analysis of small-molecule crystal structures. We investigated this phenomenon using calculations on simplified active site models. A recent paper suggested that several aspects of the analysis required further exploration. In this paper we: (i) review the results of our crystallographic study; (ii) report molecular dynamics studies which investigate the effect of protein movement; (iii) report ONIOM calculations which trace the reaction coordinate for an oxyanion hole reaction in the presence of a complete enzyme active site. These results show that the limitations of gas phase calculations on simplified models do not invalidate our comparison of competing active site geometries. These new results reaffirm the conclusion that oxyanion holes are not usually stabilized by planar arrangements of H-bonds, and that this sub-optimal transition state stabilization leads to better overall catalysis.

Graphical abstract: Hydrogen-bond stabilization in oxyanion holes: grand jeté to three dimensions

Back to tab navigation

Supplementary files

Publication details

The article was received on 11 Oct 2011, accepted on 23 Dec 2011 and first published on 23 Dec 2011


Article type: Paper
DOI: 10.1039/C2OB06717J
Citation: Org. Biomol. Chem., 2012,10, 1905-1913
  •   Request permissions

    Hydrogen-bond stabilization in oxyanion holes: grand jeté to three dimensions

    L. Simón and J. M. Goodman, Org. Biomol. Chem., 2012, 10, 1905
    DOI: 10.1039/C2OB06717J

Search articles by author

Spotlight

Advertisements