نمایش مختصر رکورد

dc.contributor.authorBaghban, Roghayyehen_US
dc.contributor.authorFarajnia, Safaren_US
dc.contributor.authorGhasemi, Younesen_US
dc.contributor.authorMortazavi, Mojtabaen_US
dc.contributor.authorGhasemali, Samanehen_US
dc.contributor.authorZakariazadeh, Mostafaen_US
dc.contributor.authorZarghami, Nosratollahen_US
dc.contributor.authorSamadi, Nasseren_US
dc.date.accessioned1400-08-25T00:14:08Zfa_IR
dc.date.accessioned2021-11-16T00:14:09Z
dc.date.available1400-08-25T00:14:08Zfa_IR
dc.date.available2021-11-16T00:14:09Z
dc.date.issued2021-11-01en_US
dc.date.issued1400-08-10fa_IR
dc.date.submitted2020-06-20en_US
dc.date.submitted1399-03-31fa_IR
dc.identifier.citationBaghban, Roghayyeh, Farajnia, Safar, Ghasemi, Younes, Mortazavi, Mojtaba, Ghasemali, Samaneh, Zakariazadeh, Mostafa, Zarghami, Nosratollah, Samadi, Nasser. (2021). Engineering of Ocriplasmin Variants by Bioinformatics Methods for the Reduction of Proteolytic and Autolytic Activities. Iranian Journal of Medical Sciences, 46(6), 454-467. doi: 10.30476/ijms.2020.86984.1705en_US
dc.identifier.issn0253-0716
dc.identifier.issn1735-3688
dc.identifier.urihttps://dx.doi.org/10.30476/ijms.2020.86984.1705
dc.identifier.urihttps://ijms.sums.ac.ir/article_47440.html
dc.identifier.urihttps://iranjournals.nlai.ir/handle/123456789/843145
dc.description.abstractBackground: Ocriplasmin has been developed for the induction of posterior vitreous detachment in patients with vitreomacular adhesion. At physiological pH, ocriplasmin is susceptible to autolytic and proteolytic degradation, limiting its activity duration. These undesirable properties of ocriplasmin can be reduced by site-directed mutagenesis, so that its enzymatic activities can be augmented. This study aimed to design ocriplasmin variants with improved biological/physicochemical characteristics via bioinformatics tools. Methods: This study was performed in Tabriz University of Medical Sciences, Tabriz, Iran, 2019. Through site-directed mutagenesis, three ocriplasmin variants were designed. Structural analysis was performed on the wild-type variant and the mutant variants using the Protein Interactions Calculator (PIC) server. The interactions between the S-2403 substrate and the ocriplasmin variants were studied by molecular docking simulations, and binding capability was evaluated by the calculation of free binding energy. The conformational features of protein-substrate complex systems for all the variants were evaluated using molecular dynamic simulations at 100 nanoseconds.Results: The structural analysis of ocriplasmin revealed that the substitution of threonine for alanine 59 significantly reduced proteolytic activity, while the substitution of glutamic acid for lysine 156 influenced autolytic function. The molecular docking simulation results indicated the appropriate binding of the substrate to the ocriplasmin variants with high-to-low affinities. The binding affinity of the wild-type variant for the substrate was higher than that between the mutant variants and the substrate. Simulation analyses, consisting of the root-mean-square deviation, the root-mean-square fluctuation, and the center-of-mass average distance showed a higher affinity of the substrate for the wild type than for the mutant variants. Conclusion: The mutational analysis of ocriplasmin revealed that A59T and K156E mutagenesis could be used for the development of a new variant with higher therapeutic efficacy.en_US
dc.format.extent3564
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoen_US
dc.publisherShiraz University of Medical Sciencesen_US
dc.relation.ispartofIranian Journal of Medical Sciencesen_US
dc.relation.isversionofhttps://dx.doi.org/10.30476/ijms.2020.86984.1705
dc.subjectMutagenesisen_US
dc.subjectSite-directeden_US
dc.subjectMolecular docking simulationen_US
dc.subjectMolecular dynamics simulationen_US
dc.titleEngineering of Ocriplasmin Variants by Bioinformatics Methods for the Reduction of Proteolytic and Autolytic Activitiesen_US
dc.typeTexten_US
dc.typeOriginal Article(s)en_US
dc.contributor.departmentDepartment of Medical Biotechnology, School of Advanced Medical Science, Tabriz University of Medical Sciences,Tabriz, Iranen_US
dc.contributor.departmentDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iranen_US
dc.contributor.departmentPharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iranen_US
dc.contributor.departmentDepartment of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iranen_US
dc.contributor.departmentDepartment of Medical Biotechnology, School of Advanced Medical Science, Tabriz University of Medical Sciences,Tabriz, Iranen_US
dc.contributor.departmentDepartment of Biology, Payame Noor University, Tehran, Iranen_US
dc.contributor.departmentDepartment of Medical Biotechnology, School of Advanced Medical Science, Tabriz University of Medical Sciences,Tabriz, Iranen_US
dc.contributor.departmentDepartment of Medical Biotechnology, School of Advanced Medical Science, Tabriz University of Medical Sciences,Tabriz, Iranen_US
dc.citation.volume46
dc.citation.issue6
dc.citation.spage454
dc.citation.epage467
nlai.contributor.orcid0000-0002-5732-2778
nlai.contributor.orcid0000-0002-6087-9147
nlai.contributor.orcid0000-0003-4172-0672


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