A structurally conserved water molecule in Rossmann dinucleotide‐binding domains

作者：Christopher A. Bottoms, Paul E. Smith, John J. Tanner · 发表于：Protein Science · 年份：2002 · DOI：10.1110/ps.0213502 · 被引用次数：151 · 研究领域：DNA and Nucleic Acid Chemistry、Enzyme Structure and Function、Biochemical and Molecular Research

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.