title: Computational analysis of TRAPPC9: candidate gene for autosomal recessive non-syndromic mental retardation.
abstract: Mental retardation (MR)/ intellectual disability (ID) is a neuro-developmental disorder characterized by a low intellectual quotient (IQ) and deficits in adaptive behavior related to everyday life tasks such as delayed language acquisition, social skills or self-help skills with onset before age 18. To date, a few genes (PRSS12, CRBN, CC2D1A, GRIK2, TUSC3, TRAPPC9, TECR, ST3GAL3, MED23, MAN1B1, NSUN1) for autosomal-recessive forms of non syndromic MR (NS-ARMR) have been identified and established in various families with ID. The recently reported candidate gene TRAPPC9 was selected for computational analysis to explore its potentially important role in pathology as it is the only gene for ID reported in more than five different familial cases worldwide. YASARA (12.4.1) was utilized to generate three dimensional structures of the candidate gene TRAPPC9. Hybrid structure prediction was employed. Crystal Structure of a Conserved Metalloprotein From Bacillus Cereus (3D19-C) was selected as best suitable template using position-specific iteration-BLAST. Template (3D19-C) parameters were based on E-value, Z-score and resolution and quality score of 0.32, -1.152, 2.30°A and 0.684 respectively. Model reliability showed 93.1% residues placed in the most favored region with 96.684 quality factor, and overall 0.20 G-factor (dihedrals 0.06 and covalent 0.39 respectively). Protein-Protein docking analysis demonstrated that TRAPPC9 showed strong interactions of the amino acid residues S(253), S(251), Y(256), G(243), D(131) with R(105), Q(425), W(226), N(255), S(233), its functional partner 1KBKB. Protein-protein interacting residues could facilitate the exploration of structural and functional outcomes of wild type and mutated TRAPCC9 protein. Actively involved residues can be used to elucidate the binding properties of the protein, and to develop drug therapy for NS-ARMR patients.
authors.forename: Naureen Aslam
authors.initials: NA
authors.lastname: Khattak
authors.affiliation: Department of Biochemistry, PMAS-Arid agriculture university, Rawalpindi, Pakistan.. naureen.aslam@uaar.edu.pk.
authors.forename: Asif
authors.initials: A
authors.lastname: Mir
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics*; D005808:Genes, Recessive; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry; D008607:Intellectual Disability / Q000188:drug therapy / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009154:Mutation; D010802:Phylogeny; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012984:Software
chemical_list: D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; C503887:TRAPPC9 protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human