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Phosphoryl transfer by a concerted reaction mechanism in UMP/CMP-kinase.

Authors
  • Hutter, M C
  • Helms, V
Type
Published Article
Journal
Protein science : a publication of the Protein Society
Publication Date
Nov 01, 2000
Volume
9
Issue
11
Pages
2225–2231
Identifiers
PMID: 11152133
Source
Medline
License
Unknown

Abstract

The reaction mechanism of phosphoryl transfer catalyzed by UMP/CMP-kinase from Dictyostelium discoideum was investigated by semiempirical AM1 molecular orbital computations of an active site model system derived from crystal structures that contain a transition state analog or a bisubstrate inhibitor. The computational results suggest that the nucleoside monophosphate must be protonated for the forward reaction while it is unprotonated in the presence of aluminium fluoride, a popular transition state analog for phosphoryl transfer reactions. Furthermore, a compactification of the active site model system during the reaction and for the corresponding complex containing AlF3 was observed. For the active site residues that are part of the LID domain, conformational flexibility during the reaction proved to be crucial. On the basis of the calculations, a concerted phosphoryl transfer mechanism is suggested that involves the synchronous shift of a proton from the monophosphate to the transferred PO3-group. The proposed mechanism is thus analogous to the phosphoryl transfer mechanism in cAMP-dependent protein kinase that phosphorylates the hydroxyl groups of serine residues.

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