Shamila Alipoor Astaneh; Zarrin Minuchehr; Armin Madadkar-Sobhani; Mehran Miroliaei
Abstract
A progressive computational analysis of available sequence and crystal structure data was used to identify functionally and structurally important residues in medium-chain Alcohol dehydrogenases super family throughout evolution. Altman and Gretsine core finding method was used to identify a core set ...
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A progressive computational analysis of available sequence and crystal structure data was used to identify functionally and structurally important residues in medium-chain Alcohol dehydrogenases super family throughout evolution. Altman and Gretsine core finding method was used to identify a core set of atoms with low structural variability. With further analysis of core regions in ADHs (solvent exposure and number of contacts) and also sequential analysis, we could infer the common properties of highly conserved positions in ADHs. The sequential analysis was done with respect to some special properties of amino acids in order to derive the level of conservation. The core structure analysis was re-judged in light of sequential analysis. Sixty percent of the core positions correspond to the highly conserved positions that were found by the sequence analysis.It seems that the core positions in ADHs are responsible for the maintenance of structural integrity and also contribute to the active site. Location of rigid parts of structures in catalytic domain may help to minimize the thermal fluctuation effect on substrate binding and would probably keep the structure in a good condition. Our data supports that it is possible to define patterns of conservity in some important region in sequence of Alcohol dehydrogenase and explain patterns of structural stability which are necessary for overcoming throughout evolution.
Shiva Kalantari; Mohammad ataghi zadeh; Maasoumeh Dehghani; Armin Madadkar sobhani; Mostafa Rezaiee tavirani
Abstract
Background and aim: Rab23 is a member of the Rab family of proteins that regulate the fusion and docking of vesicle membranes to membrane of eukaryotic cells. This protein is a spontaneous negative regulator of hedgehog signaling in vertebrates. Hedgehog signaling has a critical role in tissue and organs ...
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Background and aim: Rab23 is a member of the Rab family of proteins that regulate the fusion and docking of vesicle membranes to membrane of eukaryotic cells. This protein is a spontaneous negative regulator of hedgehog signaling in vertebrates. Hedgehog signaling has a critical role in tissue and organs of vertebrates which has associate with congenital disorders and many types of tumors. Therefore, inclusion of Rab23 is suggested in this pathway and expression anomalies. Mutation of the gene of Rab23 and abnormal expression of this protein can cause some diseases such as: Gorlin and Carpenter syndrome, thyroid carcinoma, hepatocell carcinoma, tumors and different types of cancers.
Matherial and methods: Modelling of this protein was done via Modeller9V7 by selection a suitable template with high similarity fom PDB database. The best model was selected by Procheck for simulation step and then molecular dynamic simulation was done via GROMACS. Autodock4.2 was used for docking analysis of Rab23 with cholesterol for determination of binding sites.
Results: Stability of RMSD and energy plot showed that the constructed 3D model is stable and close to reality. Docking analysis displayed some binding sites for cholesterol.
Conclusion: Having binding site for cholesterol suggests that this protein performes its role in docking to vesicle memberane through the region possesed cholesterol in association with other proteins such as GLI2 and GLI3. Owing to biological importance of Rab23, simulation of this protein in silico could be beneficial for therapeutic purposes in drug design and/or inhibitory ligands. Ling, molecular dynamic simulation
