In silico analysis of single nucleotide polymorphisms in the regulatory and coding region of mmp-7 encoding gene.
,1,* Majid tafrihi
1. Molecular & Cell Biology Research Lab 2, Department of Molecular and Cell Biology, Faculty of Sciences, University of Mazandaran, Babolsar, Mazandaran, Iran; P.O.
2. Molecular & Cell Biology Research Lab 2, Department of Molecular and Cell Biology, Faculty of Sciences, University of Mazandaran, Babolsar, Mazandaran, Iran; P.O.
Introduction: matrix metalloproteinases (mmps) are one of the main group of enzymes degrading collagen and other protein degradation in extracellular matrix (ecm). mmp-7 (or matrilysin) is the smallest mmp, localized on chromosome 11q21-q22, which can degrade elastin, proteoglycans, fibronectin and type iv collagen. in this work, we explored the potential of structure according to in silico analyses to investigate the impact of two missense mutations, rs372470873 (l246r) and rs763277489 (w104r) on the structure and function of mmp-7. also we explored the possible effect of single nucleotide polymorphism in the promoter region of the mmp-7 encoding gene.
Materials and methods: in this work we used the ncbi and uniprot databases to get information about snps including snp id, amino acid position. we used online prediction servers such as sift, polyphen 2.0, i-mutant 3.0 and provean. in addition, we used snp&go, phd snp, pmut, align gv-gd, panther and netsurfp servers. to predict effect of nssnps on structure and function of protein we used cfssp, hope project online tools and chimera software, alpha version 1.12. we have used snpinspector and matinspector tools to analyze the effects of rs11568818 on tfs binding site of promoter region mmp-7 encoding gene.
Results: analyses using sift, polyphen 2.0, i-mutant 3.0 ,provean, snp&go, phd snp, pmut, align gv-gd and panther demonstrate that rs372470873 (l246r) and rs763277489 (w104r) snps are deleterious and could be disease-related. the netsurfp show that class assignment for these snps does not change. structural analyses using cfssp, hope project and chimera did not show significant changes in the local structure of the protein. in another step, the snpinspector predicted one lost tf site in the + strand of the promoter region, but the matinspector did not show any evidence for this change.
Conclusion: we analyzed the effect of two snps evaluated their impact on the structure of the mmp-7 using online tools. analyzing deleterious nssnps by both sequence and structure level has the added advantage of being able to assess the reliability of the generated prediction results by cross-referencing the results from both approaches. these results demonstrate that that are likely to have functional impact on the mmp-7 gene and contribute to susceptibility to different diseases including cancer.
Keywords: matrix metalloproteinase, mmp-7, single nucleotide polymaorphism, cancer, in silico analys