Cr. Bellamacina, PROTEIN MOTIFS .9. THE NICOTINAMIDE DINUCLEOTIDE BINDING MOTIF - A COMPARISON OF NUCLEOTIDE-BINDING PROTEINS, The FASEB journal, 10(11), 1996, pp. 1257-1269
Classical nicotinamide adenine dinucleotide (NAD(+)) binding proteins
contain a beta alpha beta alpha beta unit. By comparing 14 such protei
ns, it is observed that an additional beta strand associates with this
unit to form the ''core'' topology, the minimum structure necessary t
o bind cofactor. Although the overall topologies of the cofactor bindi
ng domains of nicotinamide binding proteins vary, they all contain at
least the core topology, The first 30-35 amino acids of the core topol
ogy, called the ''fingerprint'' region, are diagnostic for the presenc
e of a dinucleotide binding fold, There are four characteristics of th
is fingerprint region: 1) a phosphate binding consensus sequence, GXGX
XG, 2) six positions usually occupied by small hydrophobic amino acids
, 3) a conserved, negatively charged residue (Glu or Asp) at the end o
f the second beta strand of the fingerprint region, and 4) a conserved
positively charged residue (Arg or Lys) at the beginning of the first
beta strand of the fingerprint region, The core topologies of the cla
ssical nicotinamide binding proteins overlap well with root mean squar
ed deviations of main chain atoms ranging from 0.7 to 4.7 Angstrom. A
conserved interaction (found in 8 of the 12 classical nicotinamide bin
ding proteins studied) between the cofactor and the protein is a hydro
gen bond between the pyrophosphate oxygen of NAD(P)(+) and the carboxy
-terminal glycine of the phosphate binding helix, the first alpha heli
x of the beta alpha beta alpha beta unit. The classical nicotinamide b
inding proteins all bind their cofactor in the same location and orien
tation, with the cofactor itself adopting a similar extended conformat
ion in every structure. Although observed less frequently than the cla
ssical fold, numerous nonclassical folding patterns are also used by p
roteins that bind NAD(P)(+).