Kasap Murat, Sazci Ali, Ergul Emel, Akpinar Gurler
Department of Medical Biology and Genetics, Faculty of Medicine, University of Kocaeli, Umuttepe, 41380 Kocaeli, Turkey.
Mol Phylogenet Evol. 2007 Mar;42(3):838-46. doi: 10.1016/j.ympev.2006.09.020. Epub 2006 Oct 7.
Methylenetetrahydrofolate reductase (MTHFR) family of proteins catalyze the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. They contain a flavin adenine dinucleotide (FAD) as the cofactor and the enzyme in eukaryotes, except in yeast, is known to be allosterically regulated by S-adenosylmethionine. Some cardiovascular diseases, neural tube defects, neuropsychiatric diseases and certain type of cancers in humans are associated with certain polymorphisms of MTHFR. Here, we analyzed 57 of MTHFR polypeptide sequences by multiple sequence alignment and determined previously unrecognized conserved residues that may have a functional or structural importance. A previously unrecognized ATP synthase motif was found in all of the examined plant MTHFRs, suggesting a different functional capability to the plant MTHFRs in addition to the known function. On a phylogenetic tree built, eukaryotic MTHFR proteins formed a clear cluster separated from prokaryotic and archeal relatives. The sequence identities among the eukaryotic MTHFRs were less divergent than the bacterial MTHFRs.
亚甲基四氢叶酸还原酶（MTHFR）家族蛋白催化5,10 - 亚甲基四氢叶酸转化为5 - 甲基四氢叶酸。它们含有黄素腺嘌呤二核苷酸（FAD）作为辅因子，并且除酵母外，真核生物中的该酶已知受S - 腺苷甲硫氨酸的变构调节。人类的一些心血管疾病、神经管缺陷、神经精神疾病和某些类型的癌症与MTHFR的某些多态性有关。在此，我们通过多序列比对分析了57个MTHFR多肽序列，并确定了以前未识别的可能具有功能或结构重要性的保守残基。在所有检测的植物MTHFR中发现了一个以前未识别的ATP合酶基序，这表明植物MTHFR除了已知功能外还具有不同的功能能力。在所构建的系统发育树上，真核生物的MTHFR蛋白形成了一个与原核生物和古细菌亲属分开的清晰聚类。真核生物MTHFR之间的序列同一性比细菌MTHFR的差异小。
