Dihydrofolate reductase from Lactobacillus casei. Stereochemistry of NADPH binding.
Dihydrofolate reductase from Lactobacillus casei. Stereochemistry of NADPH binding.
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来自干酪乳杆菌的二氢叶酸还原酶。
DOI：
10.1016/s0021-9258(18)50708-0
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
J. Kraut
中科院分区：
文献类型：
--
作者：
D. Matthews;R. A. Alden;S. Freer;N. Xuong;J. Kraut
NADPH分子以延伸构象与二氢叶酸还原酶结合。几个单独的二面角，特别是在腺嘌呤单核苷酸部分的辅酶，不同于他们的最低能量构象。辅酶的核糖磷酸部分参与许多特定的氢键和电荷-电荷相互作用。腺嘌呤环存在于一个明显的非特异性疏水裂缝中，烟酰胺环结合在一个复杂的结构腔中，腔的一个壁包括结合甲氨蝶呤的吡嗪环。当NADPH与二氢叶酸还原酶结合时，分别连接β A与α B和β F与β G的两个相当延伸的环（残基10至24和117至135）移动2至3 A。一方面，二氢叶酸还原酶的二核苷酸结合结构域与另一方面，已知结构的四种NAD+-依赖性辅酶A酶之间没有明显的总体结构同源性。然而，在两种情况下，结合都发生在平行β折叠区域的羧基边缘，该区域两侧是一对α螺旋。
The NADPH molecule binds to dihydrofolate reductase in an extended conformation. Several of the individual dihedral angles, especially in the adenine mononucleotide portion of the coenzyme, differ from their minimum energy conformations. The ribose phosphate portions of the coenzyme are involved in numerous specific hydrogen-bonded and charge-charge interactions. The adenine ring resides in an apparently nonspecific hydrophobic cleft and the nicotinamide ring is bound within an intricately constructed cavity, one wall of which includes the pyrazine ring of bound methotrexate. Two rather extended loops (residues 10 to 24 and 117 to 135) connecting beta A to alpha B and beta F to beta G, respectively, move 2 to 3 A when NADPH binds to dihydrofolate reductase. No overall structural homology is evident between the dinucleotide binding domains of dihydrofolate reductase on the one hand and the four NAD+-dependent dehydrogenases of known structure on the other. However, binding does occur in both cases at the carboxyl edge of a region of parallel beta sheet flanked by a pair of alpha helices.