The first structure of an aldehyde dehydrogenase reveals novel interactions between NAD and the Rossmann fold.
The first structure of an aldehyde dehydrogenase (ALDH) is described at 2.6 A resolution. Each subunit of the dimeric enzyme contains an NAD-binding domain, a catalytic domain and a bridging domain. At the interface of these domains is a 15 A long funnel-shaped passage with a 6 x 12 A opening leading to a putative catalytic pocket. A new mode of NAD binding, which differs substantially from the classic beta-alpha-beta binding mode associated with the 'Rossmann fold', is observed which we term the beta-alpha,beta mode. Sequence comparisons of the class 3 ALDH with other ALDHs indicate a similar polypeptide fold, novel NAD-binding mode and catalytic site for this family. A mechanism for enzymatic specificity and activity is postulated.
Liu
Z J
ZJ
Department of Biochemistry and Molecular Biology, University of Georgia, Athens 30602, USA.
Sun
Y J
YJ
Rose
J
J
Chung
Y J
YJ
Hsiao
C D
CD
Chang
W R
WR
Kuo
I
I
Perozich
J
J
Lindahl
R
R
Hempel
J
J
Wang
B C
BC
D000444:Aldehyde Dehydrogenase / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D009243:NAD; D000444:Aldehyde Dehydrogenase