a P. G. Department of Genetics , Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Science (ARIBAS) , New Vallabh Vidyanagar , India.
Syst Biol Reprod Med. 2019 Aug;65(4):288-300. doi: 10.1080/19396368.2019.1568611. Epub 2019 Jan 24.
Methionine synthase encoded by the gene is one of the key enzymes involved in the SAM (S- Adenosyl Methionine) cycle catalyzing the conversion of homocysteine to methionine. Methionine plays an important role in the DNA, RNA, protein, phospholipids, and neurotransmitters methylation. It also maintains serum homocysteine level and indirectly regulates nucleotide synthesis and repair. The current study predicted the functional consequences of nsSNPs in human gene using SIFT, PolyPhen2, PROVEAN, SNAP2, PMut, nsSNPAnalyzer, PhD-SNP, SNPs&GO, I-Mutant, MuPro, and iPTREE-STAB. The PTM sites within the protein were predicted using ModPred and the phylogenetic conservations of amino acids & conserved domains of protein were predicted using ConSurf and NCBI conserved domain search tool respectively. The protein 3D structure was generated using SPARKS-X and analyzed using RAMPAGE. Structural deviation was analyzed using TM-Score. STRING analysis was preformed to predict protein-protein interactions. D621G, G682D, V744L, V766E, and R1027W were predicted to be the most deleterious nsSNPs in . R1027 was predicted to having the three PTM sites and G682 & V744 were predicted as highly conserved residues. D621G, G682D, V744L, V776E, and R1027W were predicted to be within conserved domains of methionine synthase. The G682D, V744L, V776E, and R1027W were predicted to alter protein 3D structure. STRING predicted that methionine synthase interacting with 10 different proteins. The present study predicted D621G, G682D, V744L, V766E, and R1027W as functionally and structurally significant nsSNPs in human gene. The present study can provide the significant information for further experimental analysis. cblG: methylcobalamin deficiency G; MTR: 5-methyl tetrahydrofolate-homocysteine methyl transferase; MS: methionine synthase; SAM: S-adenosyl methionine; nsSNPs: non-synonymous single nucleotide polymorphisms; OMIM: online mendelian inheritance in man; NCBI: national center for biological information; SIFT: sorting intolerant from tolerant; PolyPhen2: polymorphism phenotyping 2; PROVEAN: protein variation effect analyzer; SNPs&GO: single nucleotide polymorphisms and gene ontology; PhD-SNP: predictor of human deleterious single nucleotide polymorphisms; RI: reliability index; PTM: post translational modification; SPDBV: Swiss PDB viewer; PDB: protein data bank; RMSD: root mean square deviation; STRING: search tool for the retrieval of interacting proteins.
基因编码的蛋氨酸合成酶是参与 SAM（S-腺苷甲硫氨酸）循环的关键酶之一，催化同型半胱氨酸转化为蛋氨酸。蛋氨酸在 DNA、RNA、蛋白质、磷脂和神经递质甲基化中发挥重要作用。它还维持血清同型半胱氨酸水平，并间接调节核苷酸合成和修复。本研究使用 SIFT、PolyPhen2、PROVEAN、SNAP2、PMut、nsSNPAnalyzer、PhD-SNP、SNPs&GO、I-Mutant、MuPro 和 iPTREE-STAB 预测了人类基因中 nsSNP 的功能后果。使用 ModPred 预测蛋白质内的 PTM 位点，使用 ConSurf 和 NCBI 保守域搜索工具分别预测氨基酸和蛋白质保守域的进化保守性。使用 SPARKS-X 生成蛋白质 3D 结构，并使用 RAMPAGE 进行分析。使用 TM-Score 分析结构偏差。使用 STRING 分析预测蛋白质-蛋白质相互作用。D621G、G682D、V744L、V766E 和 R1027W 被预测为基因中最具破坏性的 nsSNP。R1027 被预测有三个 PTM 位点，G682 和 V744 被预测为高度保守的残基。D621G、G682D、V744L、V766E 和 R1027W 被预测为蛋氨酸合成酶的保守结构域内。G682D、V744L、V776E 和 R1027W 被预测会改变蛋白质 3D 结构。STRING 预测蛋氨酸合成酶与 10 种不同的蛋白质相互作用。本研究预测 D621G、G682D、V744L、V766E 和 R1027W 是人类基因中具有功能和结构意义的 nsSNP。本研究可为进一步的实验分析提供重要信息。cblG：甲基钴胺素缺乏 G；MTR：5-甲基四氢叶酸-同型半胱氨酸甲基转移酶；MS：蛋氨酸合成酶；SAM：S-腺苷甲硫氨酸；nsSNPs：非同义单核苷酸多态性；OMIM：在线孟德尔遗传人类；NCBI：国家生物信息中心；SIFT：从宽容中分辨出不可容忍；PolyPhen2：多态性表型 2；PROVEAN：蛋白质变异效应分析器；SNPs&GO：单核苷酸多态性和基因本体；PhD-SNP：人类有害单核苷酸多态性预测器；RI：可靠性指数；PTM：翻译后修饰；SPDBV：瑞士 PDB 查看器；PDB：蛋白质数据库；RMSD：均方根偏差；STRING：检索相互作用蛋白的搜索工具。
