Structural Phylogenomics: Selection Pressure Suggests the Functionally Important Residues Encoded by Cisplatin Resistance Related 9 Gene

作者: Saadia Shakir , Waqas Ahmed Waseem , Syed Khaqan Hasan , Muhammad Munir , Muhammad Rafiq Khanani

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摘要: Cisplatin Resistance Related 9 gene, CRR9, contributes towards the efficacy of chemotherapeutic drug namely cisplatin. Genetic studies have established association between CRR9 gene mutations and several cancers, but structure-function aspects encoded protein remains largely unaddressed. In present study, we constructed a consensus phylogenetic tree using maximum likelihood method after 1000 bootstrap replicates. Multiple sequence alignment selected orthologs was undertaken important variations were analyzed with reference to clade segregations spatial locations in structure models. The topology appears line relationship mammalian lineage. models representatives suggest strong uniformity as Root Mean Square Deviation which varies from 0.03A 0.14A. Both DAS server presence two novel transmembrane regions ranging Val461 Ala483 Thr490 Tyr506. showed primate specific amino acid substitutions. Importantly, these are mostly situated core part implying their structural and/or functional significance. Conclusively, study phylogenomics approach, not only illustrate architecture also delineate critically acids possible importance. Further direction site mutagenesis verify our finding assist understanding protein. Additionally, it allows contemplate new drugs for chemotherapy potentials gene.

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