Most of the dinucleotide-binding
domains have Rossmann folds. And ALDH have Rossmann fold to bind
NAD.
Most of the dinucleotide-binding
domains have Rossmann folds. And ALDH have Rossmann fold to bind
NAD.
ALDH Glu140 bind the Adenosine
ribose of NAD. And it formed some hydrogen bond and van der waals
contact.
ALDH has a NAD-binding Rossmann
fold is located in £]4 -£\D-£]2.
Rossmann fold £] -£\-£] and
£] -£\-£] -£\-£]
ALDH and ADH use different
residue interact with NAD
ALDH use Glu140
to have contact with NAD.
But ADH use Asp223
to bind NAD
Helix £\A has been termed the" dinucleotide -binding helix" since its
helix dipole provides a favourable interaction with the nagtive charged
pyrophosphate moiety of the dinucleotide. The fingerprint sequence
is GXGXXG is often in £]1-£\A loop , and it
is the classic way. So ALDH and ADH have different fasion binding NAD.
ALDH have new NAD-binding Rossmann
fold
The binding Rossmann fold
of ALDH and ADH.
ALDH(left)
£]4 -£\D-£]2
term as :£]-£\,£]
ADH(right)
£]1-£\A-£]2
term as :£]-£\-£]
Classic
NAD-binding fingerprint
In classic NAD-binding Rossmann fold, and sequence is conserved call a fingerprint sequence :
Gly-X-Gly-X-X-Gly(G1-X-G2-X-X-G3)
These three Gly position in
classic fasion have different meaning in structure
The Ramachandran Plot of these 3 Gly position of the fingerprint sequence:
The first Gly G1 allows for a tight turn of the main chain with special(£p,£r) angels.
G2 allows the coenzyme to pack close to £\A producing a favourable charge-dipole interaction. Also because steric hindrance with the bound dinucleotide would occur with a side chain at this position.
G3 residue is important to provide space for a close interaction between the £] strands and £\ helix.
ALDH have new
NAD-binding fingerprint sequence:
ALDH NAD-binding fingerprint sequence is--
GXTXXG
but this figerprint sequence is located at £]4 -£\D, not £]1-£\A. Just see the sequence bellow-- (b)
The figerprint is an Rossmann fold, but ALDH loss the fingerprint in £]1-£\A-£]2 fold. And changes to £]4 -£\D-£]2 . And the sequence is different form classic way.
The (c) shown the ALDH disappeared the fingerprint sequence in £]1-£\A.
1. ALDH has a new NAD-binding Rossmann fold
, and it is different from classic NAD-binding Rossmann fold , such as
Alcohol DHase .
2. ALDH NAD-binding fingerprint is G-X-T-X-X-G.
ADH NAD-binding fingerprint
is G-X-G-X-X-G
3. ALDH family have a conserved residue
Glu140, and Glu140 forms H-bond to adenosine ribose of
NAD.
Reference:
1. Jones, K.H., Lindhahl, R., Baker, D.C. & Timkovich, R. Hydride transfer stereospecificity of rat liver aldehyde dehydrogenase. J. Bio. Chem.262, 11911-11913(1987)
2. Wierenga, R.K. , De Maeyer , M.C. , & Hol, W.G.J. Interaction of pyrophosphate moieties with £\ helix in dinucleotide binding proteins. Biochemistry 24, 1346-1357(1985).
3. Wierenga, R.K., Terpstra, P. & Hol, W.G.J. Prediction of the occurance of the ADP-binding £]£\£]-fold in proteins, using an amino acid fingerprint. J. Bio. Chem. 187, 101-107(1986).
4. Farres, J. et al. Investigation of the active site cysteine residue of rat liver mitochondial aldehyde dehydrogenase by site-directed mutagenesis. Biochemistry 34, 2592-2598(1995).
5.von Bahr-Lindstrom, H. et al . Characterization of the coenzyme binding site of lin\ver aldehyde dehydrogenase: different reactivity of coenzyme analogs.Biochemistry 24, 5847-5851(1985).
6. Jacoby, W.B. & Ziegler, D.M. Enzymes of detoxication. J.
Bio. Chem. 265, 20715-20718(1990).
1999/1/11 Matthew J. Wu