Inositol Monophosphatase: A Bifunctional Enzyme in Mycobacterium smegmatis.

Inositol Monophosphatase: A Bifunctional Enzyme in Mycobacterium smegmatis.
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DOI:
10.1021/acsomega.8b01753
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发表时间:
2018-10-31
期刊:
影响因子:
4.1
通讯作者:
Movahedzadeh F
Movahedzadeh F
中科院分区:
化学3区
文献类型:
--
作者:
Goswami R;Bondoc JMG;Wheeler PR;Jafari A;Gonzalez T;Mehboob S;Movahedzadeh F

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肌醇单磷酸酶(IMP酶)是合成磷脂酰肌醇的关键酶,磷脂酰肌醇是分枝杆菌细胞壁的重要组成部分。来自耻垢分枝杆菌的IMPA酶A(ImpA)是一种双功能酶,其也作为果糖-1,6-二磷酸酶(FBPase)发挥作用。为了更好地理解该酶的双功能性质,对几个关键残基进行点诱变,并测试其酶活性。我们的研究结果沿着活性位点模型支持这样一个事实,即ImpA是一种双功能酶,其中残基Gly 94、Thr 95被假设为对FBPase活性有贡献,残基Trp 220、Asp 221被假设为对IMP酶活性有贡献。与单突变体相比,双突变体W220 A + D221 A显著降低了FBPase和IMP酶活性,而双突变体G94 A + T95 A令人惊讶地部分恢复了IMP酶活性。这项研究为更好地了解这种酶的双功能性质奠定了基础。
Inositol monophosphatase (IMPase) is a crucial enzyme for the biosynthesis of phosphatidylinositol, an essential component in mycobacterial cell walls. IMPase A (ImpA) from Mycobacterium smegmatis is a bifunctional enzyme that also functions as a fructose-1,6-bisphosphatase (FBPase). To better understand the bifunctional nature of this enzyme, point mutagenesis was conducted on several key residues and their enzyme activity was tested. Our results along with active site models support the fact that ImpA is a bifunctional enzyme with residues Gly94, Thr95 hypothesized to be contributing to the FBPase activity and residues Trp220, Asp221 hypothesized to be contributing to the IMPase activity. Double mutants, W220A + D221A reduced both FBPase and IMPase activity drastically while the double mutant G94A + T95A surprisingly partially restored the IMPase activity compared to the single mutants. This study establishes the foundation toward obtaining a better understanding of the bifunctional nature of this enzyme.
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