Analysis of nucleotide diphosphate sugar dehydrogenases reveals family and group-specific relationships.
Analysis of nucleotide diphosphate sugar dehydrogenases reveals family and group-specific relationships.
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DOI：
10.1002/2211-5463.12022
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发表时间：
2016-01
期刊：
影响因子：
2.6
通讯作者：
Perozich J
中科院分区：
文献类型：
--
作者：
Freas N;Newton P;Perozich J
UDP-葡萄糖脱氢酶（UDPGDH）、UDP-N-乙酰甘露糖胺脱氢酶（UDPNAMDH）和GDP-甘露糖脱氢酶（GDPMDH）属于NAD +连接的4电子转移氧化还原酶家族，称为核苷酸二磷酸糖脱氢酶（NDP-SDH）。UDPGDH是一种负责将UDP-d-葡萄糖转化为UDP-d-葡萄糖醛酸的酶，UDP-d-葡萄糖醛酸是一种根据其所发现的生物体而具有不同作用的产物。UDPNAMDH和GDPMDH通过与UDPGDH相似的机制分别将UDP-N-乙酰基-甘露糖胺转化为UDP-N-乙酰基-甘露糖胺糖醛酸和将GDP-甘露糖转化为GDP-甘露糖醛酸。他们的产品被用作铜绿假单胞菌和金黄色葡萄球菌等生物体中发现的胞外多糖的基本组成部分。很少有研究调查这些酶之间的关系。本研究通过分析229个氨基酸序列揭示了这三种酶之间的关系。鉴定出18个不变残基和其他几个高度保守的残基，每个残基在维持酶结构、辅酶结合或催化功能方面发挥关键作用。此外，10个保守的模体，其中包括大多数的保守残基进行了鉴定，并提出了他们的作用。系统发育树显示了每个组之间的关系和验证组分配。最后，组熵分析确定了每个NDP-SDH组特有的新保守性，包括对NDP-糖底物相互作用，酶结构和亚基间接触至关重要的残基位置。这些位置可以作为未来研究的目标。 UDP-葡萄糖脱氢酶（UDPGDH，EC 1.1.1.22）。
UDP‐glucose dehydrogenase (UDPGDH), UDP‐N‐acetyl‐mannosamine dehydrogenase (UDPNAMDH) and GDP‐mannose dehydrogenase (GDPMDH) belong to a family of NAD +‐linked 4‐electron‐transfering oxidoreductases called nucleotide diphosphate sugar dehydrogenases (NDP‐SDHs). UDPGDH is an enzyme responsible for converting UDP‐d‐glucose to UDP‐d‐glucuronic acid, a product that has different roles depending on the organism in which it is found. UDPNAMDH and GDPMDH convert UDP‐N‐acetyl‐mannosamine to UDP‐N‐acetyl‐mannosaminuronic acid and GDP‐mannose to GDP‐mannuronic acid, respectively, by a similar mechanism to UDPGDH. Their products are used as essential building blocks for the exopolysaccharides found in organisms like Pseudomonas aeruginosa and Staphylococcus aureus. Few studies have investigated the relationships between these enzymes. This study reveals the relationships between the three enzymes by analysing 229 amino acid sequences. Eighteen invariant and several other highly conserved residues were identified, each serving critical roles in maintaining enzyme structure, coenzyme binding or catalytic function. Also, 10 conserved motifs that included most of the conserved residues were identified and their roles proposed. A phylogenetic tree demonstrated relationships between each group and verified group assignment. Finally, group entropy analysis identified novel conservations unique to each NDP‐SDH group, including residue positions critical to NDP‐sugar substrate interaction, enzyme structure and intersubunit contact. These positions may serve as targets for future research. UDP‐glucose dehydrogenase (UDPGDH, EC 1.1.1.22).