title: In silico analyses of COMT, an important signaling cascade of dopaminergic neurotransmission pathway, for drug development of Parkinson's disease.
abstract: Catechol-O-methyltransferase (COMT) has a vital role for degradation of dopamine, a neurotransmitter, and this dopamine performs an important function in our mental and physical health. The scarcity of dopamine may lead to Parkinson's disease, and inhibition of COMT can stop dopamine metabolism. Here, we have carried out genomics and proteomics analyses of COMT in order to facilitate new inhibitors of COMT. For genomics analyses, we performed codon composition investigation of COMT gene which shows A+T content which is 53.3 %. For proteomics analyses, conservation patterns and residues (highly conserved amino acids GLU64, LEU65, GLY66, CYS69, GLY70, ALA77, GLU90, THR99, SER119, ASP136, LEU140, ASP141, THR164, ASN170, VAL171, and ILE172), binding grooves, binding pockets, binding and conformation with substrate, evaluation of amino acid composition (15 % leucine rich), high scoring hydrophobic segments, high scoring transmembrane segments, tandem and periodic repeats, and disulfide bonds (three numbers), sequence logos (maximum stack height of 3 b and minimum stack height of <0.5 b) have been investigated for COMT protein. Furthermore, using COMT sequences of different species (class Mammalia, class Amphibia, and class Pisces), a phylogenetic tree has been constructed to examine the evolutionary relationship among different species.
authors.affiliation: Centre for Nanobiotechnology, Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore, India. drchiranjib@yahoo.com
authors.forename: Chiranjib
authors.initials: C
authors.lastname: Chakraborty
authors.forename: Soumen
authors.initials: S
authors.lastname: Pal
authors.forename: C George Priya
authors.initials: CG
authors.lastname: Doss
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.forename: Chan-Shing
authors.initials: CS
authors.lastname: Lin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D003062:Codon / Q000235:genetics; D019295:Computational Biology; D017124:Conserved Sequence; D004220:Disulfides / Q000737:chemistry; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000473:pathology; D055808:Drug Discovery; D019143:Evolution, Molecular; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010802:Phylogeny; D017433:Protein Structure, Secondary; D013499:Surface Properties; D009435:Synaptic Transmission
chemical_list: D003062:Codon; D004220:Disulfides; D002394:Catechol O-Methyltransferase