PatternQuery
Find atom patterns in molecular databases

Each zinc finger spans ~30 amino acid residues and folds into a simple ββα-motif around a tetrahedrally coordinated zinc ion. The motif can be identified by a regular expression X₂-C-X_2,4-C-X₁₂-H-X_3,5-H_1,2, where X represents any amino acid. The X₁₂ region usually has the form: X₃-[F|Y]-X₅-Ψ-X_1,2, where Ψ denotes a hydrophobic residue [2]. The zinc ion is coordinated by two cysteine residues and two histidines.

PQ was employed in the discovery and extraction of all structural patterns which satisfy the sequence condition. In total, 354 patterns representing zinc fingers were successfully identified in 233 distinct PDB entries. The majority of patterns come from Homo sapiens and other mammals.

1. Gupta, A., Christensen, R.G., Bell, H.A., Goodwin, M., Patel, R.Y., Pandey, M., Enuameh, M.S., Rayla, A.L., Zhu, C., Thibodeau-Beganny, S., et al. (2014) An improved predictive recognition model for Cys(2)-His(2) zinc finger proteins. Nucleic Acids Res., 42, 4800–12.
2. Pabo, C.O., Peisach, E. and Grant, R.A. (2001) Design and selection of novel Cys2His2 zinc finger proteins. Annu. Rev. Biochem., 70, 313–40.

We employed MQ in the discovery of sugar binding sites with similar geometry as the tetrameric PA-IIL protein in the Protein Data Bank. The carbohydrate-binding domain is calcium dependent, with two calcium ions stabilizing the binding site and contributing to sugar binding [2]. Therefore, just the structures containing calcium ions were queried. The query was searching for 2 calcium ions at most 4Å far from each other, and all the residues with direct interaction with either of the ions. Furthermore, just the molecular patterns containing a furan or pyran ring were kept. Additionally, in case the phosphorus atom was present, the pattern was filtered out in order to avoid nucleotides.

The outcome of this query is made up of 87 distinct patterns originating from 36 PDB entries of 7 different organisms. The majority of them originated from P.aeruginosa, however, binding sites from other pathogens such as R. solanacearum, B. cenocepacia or C. violaceum were identified. In 83 patterns, the sugar-binding site is composed of 3x Asp, 2x Asn, 1x Glu and 1x Gly residues, in agreement with literature reports of the binding site for 24 PDB entries belonging to 3 pathogens.

1. Hauck, D., Joachim, I., Frommeyer, B., Varrot, A., Philipp, B., Möller, H.M., Imberty, A., Exner, T.E. and Titz, A: Discovery of two classes of potent glycomimetic inhibitors of Pseudomonas aeruginosa LecB with distinct binding modes. 2012, ACS Chem. Biol., 8, 1775–84.
2. Mitchell, E., Houles, C., Sudakevitz, D., Wimmerova, M., Gautier, C., Pérez, S., Wu, A.M., Gilboa-Garber, N. and Imberty, A: Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. 2012, Nat. Struct. Biol., 9, 918–21.