Crystal structure of a bifunctional aldolase-dehydrogenase: Sequestering a reactive and volatile intermediate

B.A. Manjasetty, J. Powlowski, Alice Vrielink

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81 Citations (Scopus)

Abstract

The crystal structure of the bifunctional enzyme 4-hydroxy-2-ketovalerate aldolase (DmpG)/acylating acetaldehyde dehydrogenase (DmpF), which is involved in the bacterial degradation of toxic aromatic compounds, has been determined by multiwavelength anomalous dispersion (MAD) techniques and refined to 1.7-Å resolution. Structures of the two polypeptides represent a previously unrecognized subclass of metal-dependent aldolases, and of a CoA-dependent dehydrogenase. The structure reveals a mixed state of NAD+ binding to the DmpF protomer. Domain movements associated with cofactor binding in the DmpF protomer may be correlated with channeling and activity at the DmpG protomer. In the presence of NAD+ a 29-Å-long sequestered tunnel links the two active sites. Two barriers are visible along the tunnel and suggest control points for the movement of the reactive and volatile acetaldehyde intermediate between the two active sites.
Original languageEnglish
Pages (from-to)6992-6997
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number12
DOIs
Publication statusPublished - 2003

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