Abstract # 12
Biodesign India 1.0 07-09 Oct 2010
Synopsis of Invited Talk P. Gautam
Anna University, Chennai
Title: Global metal-ion binding protein fingerprint:Possible Application in Synthetic Biology.
Metal ion binding domains are found in proteins and they facilitate many key regulatory systems in a cell. Two different approaches to identify metal-ion binding proteins have been adopted by our group. The first method involves the design of motifs specific to different metal--ions. The first work described the signatures designed based on the copper metal binding motifs in blue copper proteins. The common feature in all blue copper proteins is a trigonal planar arrangement of two nitrogen ligands (each from histidine ) and one sulphur containing thiolate ligand (from cysteine), with strong interactions between the copper center and these ligands.
We also designed putative metal binding motifs for the ions of cadmium, cobalt, zinc, arsenic, mercury, magnesium, manganese, molybdenum and nickel. A pattern search against the UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases yielded true positives in each case showing the high-specificity of the motifs. Motifs were also validated against PDB structures and site directed mutagenesis studies.
Further studies were conducted using machine learning algorithms and it was discovered that most metal-ion proteins possesed a global fingerprint. Such a method will help in identifying novel metal-ion binding proteins and proteins that do not possess a canonical metal--ion binding motif. We have used a set of physico--chemical parameters of metal--ion binding proteins encoded by the genes CzcA, CzcB and CzcD as a training set to supervised classifiers and have been able to identify several other metal ion binding
proteins leading us to believe that metal-ion binding proteins have a global fingerprint, which cannot be pinned down to a single feature of the protein sequence