The nicotinamide dinucleotide binding motif: a comparison of nucleotide binding proteins.
Classical nicotinamide adenine dinucleotide (NAD+) binding proteins contain a beta alpha beta alpha beta unit. By comparing 14 such proteins, it is observed that an additional beta strand associates with this unit to form the "core" topology, the minimum structure necessary to bind cofactor. Although the overall topologies of the cofactor binding domains of nicotinamide binding proteins vary, they all contain at least the core topology. The first 30-35 amino acids of the core topology, called the "fingerprint" region, are diagnostic for the presence of a dinucleotide binding fold. There are four characteristics of this fingerprint region: 1) a phosphate binding consensus sequence, GXGXXG, 2) six positions usually occupied by small hydrophobic amino acids, 3) a conserved, negatively charged residue (Glu or Asp) at the end of 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 classical nicotinamide binding proteins overlap well with root mean squared deviations of main chain atoms ranging from 0.7 to 4.7 A. A conserved interaction (found in 8 of the 12 classical nicotinamide binding proteins studied) between the cofactor and the protein is a hydrogen bond between the pyrophosphate oxygen of NAD(P)+ and the carboxy-terminal glycine of the phosphate binding helix, the first alpha helix of the beta alpha beta alpha beta unit. The classical nicotinamide binding proteins all bind their cofactor in the same location and orientation, with the cofactor itself adopting a similar extended conformation in every structure. Although observed less frequently than the classical fold, numerous nonclassical folding patterns are also used by proteins that bind NAD(P)+.
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Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02254-9110, USA.
D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D009243:NAD