In Silico Screening and Molecular Dynamics Simulation of Disease-Associated nsSNP in TYRP1 Gene and Its Structural Consequences in OCA3.
Oculocutaneous albinism type III (OCA3), caused by mutations of TYRP1 gene, is an autosomal recessive disorder characterized by reduced biosynthesis of melanin pigment in the hair, skin, and eyes. The TYRP1 gene encodes a protein called tyrosinaserelated protein-1 (Tyrp1). Tyrp1 is involved in maint...
| Publicado en: | BioMed Research International Vol. 2013; pp. 697051 - 697052 |
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| Autores principales: | , |
| Formato: | research Journal Article |
| Publicado: |
Wiley-Blackwell
2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104082055&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104082055 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 2013 vid: 2013 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104082055 104082055 2012190189 NLM23862152 PMC3703794 104082055 ppf: 697051 ppct: 1 formats: fmt: @attributes: type: P tig: atl: In Silico Screening and Molecular Dynamics Simulation of Disease-Associated nsSNP in TYRP1 Gene and Its Structural Consequences in OCA3. aug: au: Kamaraj, Balu Purohit, Rituraj affil: School of Bio Sciences and Technology (SBST), Bioinformatics Division, Vellore Institute of Technology University, Vellore, Tamil Nadu 632014, India. sug: subj: Albinism Computer Simulation Disease Susceptibility Membrane Glycoproteins Oxidoreductases Polymorphism, Genetic Sequence Analysis Human Proteins Software Time Factors ab: Oculocutaneous albinism type III (OCA3), caused by mutations of TYRP1 gene, is an autosomal recessive disorder characterized by reduced biosynthesis of melanin pigment in the hair, skin, and eyes. The TYRP1 gene encodes a protein called tyrosinaserelated protein-1 (Tyrp1). Tyrp1 is involved in maintaining the stability of tyrosinase protein and modulating its catalytic activity in eumelanin synthesis. Tyrp1 is also involved in maintenance of melanosome structure and affects melanocyte proliferation and cell death. In this work we implemented computational analysis to filter the most probable mutation that might be associated with OCA3. We found R326H and R356Q as most deleterious and disease associated by using PolyPhen 2.0, SIFT, PANTHER, I-mutant 3.0, PhD-SNP, SNP&GO, Pmut, and Mutpred tools. To understand the atomic arrangement in 3D space, the native and mutant (R326H and R356Q) structures were modelled. Finally the structural analyses of native and mutant Tyrp1 proteins were investigated using molecular dynamics simulation (MDS) approach. MDS results showed more flexibility in native Tyrp1 structure. Due to mutation in Tyrp1 protein, it became more rigid and might disturb the structural conformation and catalytic function of the structure and might also play a significant role in inducing OCA3. The results obtained from this study would facilitate wet-lab researches to develop a potent drug therapies against OCA3. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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