Premium
A structurally conserved water molecule in Rossmann dinucleotide‐binding domains
Author(s) -
Bottoms Christopher A.,
Smith Paul E.,
Tanner John J.
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0213502
Subject(s) - chemistry , hydrogen bond , stereochemistry , binding site , molecule , protein structure , nucleotide , crystallography , biochemistry , organic chemistry , gene
Abstract A computational comparison of 102 high‐resolution (≤1.90 Å) 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 α‐helix “A” oriented perpendicular to the β‐sheet. Thus, the conserved water molecule appears to be an inherent structural feature of the classic Rossmann dinucleotide‐binding domain.