PREDICTION OFOGG1 STRUCTURAL AND FUNCTIONAL MOTIFS WITH ACTIVE BINDING SITES FROM CAMELUS DROMEDARIES
W. Khan1*, Z. Abduljaleel2, 3, 4, *, F. A. Al-Allaf2, 3, N. Shahzad5, W. El-Huneidi1, 6, M. Elrobh7, M. Alanazi7 and Hani Faidah8, 9
1Department of Basic Sciences, P.O Box 3660, College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11426, Kingdom of Saudi Arabia; 2Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O.Box 715, Makkah 21955, Kingdom of Saudi Arabia; 3Science and Technology Unit, Umm Al Qura University, P.O. Box 715, Makkah 21955, Kingdom of Saudi Arabia; 3Molecular Diagnostics Unit, Department of Laboratory and Blood Bank, King Abdullah Medical City, Makkah 21955, Kingdom of Saudi Arabia; 4Molecular Diagnostics Unit, Al Noor Specialized Hospital P.O.Box: 6251, Makkah, Saudi Arabia; 5Department of Pharmacology and Toxicology, College of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia; 6Department of Basic Medical Sciences, College of medicine, University of Sharjah, United Arab Emirates; 7Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia;8Molecular Diagnostics Unit, Department of Laboratory and Blood Bank, Al Noor Specialized Hospital P.O.Box: 6251, Makkah, Saudi Arabia.9Department of Microbiology, College of Medicine, Umm Al-Qura University, P.O.Box: 715, Makkah 21955, Saudi Arabia.
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Many biological mechanisms involve the interaction of proteins or binding of other molecules to proteins. The precise prediction of functionally active binding sites on the protein surface could play an important role in predicting the nature of protein-protein or protein-ligand interactions. The present research was conducted on 8-oxoguanine DNA glycosylase geneOGG1 sequence from Arabian camel (camelus dromedaries) to predict the protein structure. In this study, 1790 long amiono acid (AA) sequences of OGG1 fromC. dromedarieswere used to predict its protein structure based on multiple alignments by Lometes & Illterative ITasser simulations. Because the full structure ofOGG1 protein cannot be predicted based on the homology modeling using conserved regions of other mammalian species, we predicted the 3D structure of two domains of the OGG1 protein. The two regions predicted were OGG1 protein domain 1 (D1) comprised of amino acids from 1-1000 and OGG1 protein domain 2 (D2) comprised of amino acids from 1000-1790. The 3D protein structures were validated using RAMPAGE Ramachandran plot and functional structures were predicted based on the homologous regions from other species including human, rat, mouse and panda. The functional group predications were established using the Eukaryote Linear Motif (ELM) resource. Among the important functions predicted for OGG1 proteins were LIG_BRCT_BRCA1_1 instances of Phosphopeptide motif which directly interacts with the BRCT (carboxy-terminal) domain of the breast cancer gene BRCA1, LIG_FHA_2 of Phosphothreonine motif binding a subset of FHA domains that have a preference for an acidic amino acid at the replication fork, and MOD_TYR_ITSM of the CD150 subfamily of receptors that bind to and are regulated by SH2 adaptor molecule. These sites may constitute target for drug design for many pharmaceutical and biotechnological purposes. The target site of binding region for OGG1 was predicted both in D1 and D2 by using site finder tools of Molecular Operation Environment (MOE). Furthermore, the results also predicted two conserved regions, both 45AA long, having 100.0% similarity with the crystal structure of Calmodium-Dependent Protein Kinase I (CaM kinase I) from rat (Q63450). This is the first report that deals with the Arabian camelOGG1protein structure prediction along with functional motifs and binding sites identification.
Keywords: Camelus dromedaries, OGG1 gene, Homology Modeling; Protein Validation; Binding site Prediction, Functional group Prediction, Multiple Sequence Alignments.