A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
A computational comparison of 102 high-resolution (</=1.90 A) enzyme-dinucleotide (NAD, NADP, FAD) complexes was performed to investigate the role of solvent in dinucleotide recognition by Rossmann fold domains. The typical binding site contains about 9-12 water molecules, and about 30% of the hydrogen bonds between the protein and the dinucleotide are water mediated. Detailed inspection of the structures reveals a structurally conserved water molecule bridging dinucleotides with the well-known glycine-rich phosphate-binding loop. This water molecule displays a conserved hydrogen-bonding pattern. It forms hydrogen bonds to the dinucleotide pyrophosphate, two of the three conserved glycine residues of the phosphate-binding loop, and a residue at the C-terminus of strand four of the Rossmann fold. The conserved water molecule is also present in high-resolution structures of apo enzymes. However, the water molecule is not present in structures displaying significant deviations from the classic Rossmann fold motif, such as having nonstandard topology, containing a very short phosphate-binding loop, or having alpha-helix "A" oriented perpendicular to the beta-sheet. Thus, the conserved water molecule appears to be an inherent structural feature of the classic Rossmann dinucleotide-binding domain.
Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211, USA.
Christopher A
CA
Bottoms
Paul E
PE
Smith
John J
JJ
Tanner
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D009243:NAD / Q000737:chemistry*; D009249:NADP / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D015800:Protozoan Proteins / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D001426:Bacterial Proteins; D005656:Fungal Proteins; D010940:Plant Proteins; D015800:Protozoan Proteins; D012997:Solvents; D014867:Water; D009243:NAD; D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D005998:Glycine