|Journal of Biological Chemistry (2004) 279(13):13148-55|
|Northeast Structural Genomics Consortium|
(click to unfold)
Escherichia coli YiaK catalyzes the reduction of 2,3-diketo-L-gulonate in the presence of NADH. ...
It belongs to a large family of oxidoreductases that is conserved in archaea, bacteria, and eukaryotes but shows no sequence homology to other proteins. We report here the crystal structures at up to 2.0-A resolution of YiaK alone and in complex with NAD-tartrate. YiaK has a new polypeptide backbone fold and a novel mode of recognizing the NAD cofactor. In addition, NAD is bound in an unusual conformation, at the interface of a dimer of the enzyme. The crystallographic analysis unexpectedly revealed the binding of tartrate in the active site. Enzyme kinetics studies confirm that tartrate and the related D-malate are inhibitors of YiaK. In contrast to most other enzymes where substrate binding produces a more closed conformation, the binding of NAD-tartrate to YiaK produces a more open active site. The free enzyme conformation is incompatible with NAD binding. His(44) is likely the catalytic residue of the enzyme.
|chemistry metabolism |
|Crystallography, X-Ray Sugar Acids Tartrates Protein Structure, Tertiary Escherichia coli Dimerization Protein Conformation Sugar Alcohol Dehydrogenases Catalytic Domain Models, Chemical Binding Sites Amino Acid Sequence Sequence Homology, Amino Acid Escherichia coli Proteins Models, Molecular NAD Molecular Sequence Data Kinetics Electrons Protein Binding |
|10 (Last update: 04/01/2017 11:29:57am)|
|J Biol Chem. 2004 Mar 26;279(13):13148-55. Epub 2004 Jan 12.|