Structural basis of diverse substrate recognition by the enzyme PMM/PGM from P-aeruginosa
Structural basis of diverse substrate recognition by the enzyme PMM/PGM from P-aeruginosa
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DOI：
10.1016/j.str.2003.11.015
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发表时间：
2004-01-01
期刊：
影响因子：
5.7
通讯作者：
Beamer, LJ
中科院分区：
文献类型：
--
作者：
Regni, C;Naught, L;Beamer, LJ
磷酸甘露糖变位酶/磷酸葡萄糖变位酶 (PMM/PGM) 的酶-底物复合物揭示了该酶在催化中使用四种不同底物的能力的结构基础。葡萄糖 1-磷酸、葡萄糖 6-磷酸、甘露糖 1-磷酸和甘露糖 6-磷酸的高分辨率结构表明，每个底物的磷酸基团的位置通过保守的氢键网络保持恒定。这对 1-磷酸和 6-磷酸糖的糖环产生两种不同且相互排斥的结合方向。两个方向的特异性结合是通过与糖的 O3 和 O4 羟基的关键接触来完成的，糖的 O3 和 O4 羟基必须占据赤道位置。葡萄糖和甘露糖磷酸糖的双重识别使用特异性蛋白质接触和非特异性溶剂接触的组合。 PMM/PGM 在单个活性位点容纳这四种不同底物的能力与其高度可逆的磷酰基转移反应一致，并使其能够在铜绿假单胞菌的多种生物合成途径中发挥作用。
Enzyme-substrate complexes of phosphomannomutase/ phosphoglucomutase, (PMM/PGM) reveal the structural basis of the enzyme's ability to use four different substrates in catalysis. High-resolution structures with glucose 1-phosphate, glucose 6-phosphate, mannose 1-phosphate, and mannose 6-phosphate show that the position of the phosphate group of each substrate is held constant by a conserved network of hydrogen bonds. This produces two distinct, and mutually exclusive, binding orientations for the sugar rings of the 1-phospho and 6-phospho sugars. Specific binding of both orientations is accomplished by key contacts with the O3 and O4 hydroxyls of the sugar, which must occupy equatorial positions. Dual recognition of glucose and mannose phosphosugars uses a combination of specific protein contacts and nonspecific solvent contacts. The ability of PMM/PGM to accommodate these four diverse substrates in a single active site is consistent with its highly reversible phosphoryl transfer reaction and allows it to function in multiple biosynthetic pathways in P. aeruginosa.