The inter-ligand Overhauser effect: A powerful new NMR approach for mapping structural relationships of macromolecular ligands
The inter-ligand Overhauser effect: A powerful new NMR approach for mapping structural relationships of macromolecular ligands
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DOI：
10.1023/a:1008360208627
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发表时间：
1999-09-01
影响因子：
2.7
通讯作者：
London, RE
中科院分区：
文献类型：
--
作者：
Li, DW;DeRose, EF;London, RE
通过交换将构象信息从结合态转移到未络合态的NMR实验已经使用了很多年。这里证明了存在于与酶或其他大分子受体的三元复合物中的配体间NOE（“NOE”）可以通过交换转移到未复合的配体对。这种方法通过在猪心乳酸脱氢酶存在下的乙醇酸+ NAD（+）和在L.肠系膜葡萄糖-6-磷酸脱氢酶。这一策略开辟了一个通用的方法，探索酶的活性位点和人工配体的发展，可以作为抑制剂，或更一般地作为蛋白质功能的修饰剂。
NMR experiments that transfer conformational information from the bound to the uncomplexed state via exchange have been utilized for many years. It is demonstrated here that inter-ligand NOEs ('ILOEs'), which exist in ternary complexes with enzymes or other macromolecular receptors, can be transferred via exchange to pairs of uncomplexed ligands. This approach is illustrated by studies of glycolate + NAD(+) in the presence of porcine heart lactate dehydrogenase, and by glucose-6-phosphate + NADPH in the presence of L. mesenteroides glucose-6-phosphate dehydrogenase. This strategy opens up a general methodology for exploring the active sites of enzymes and for the development of artificial ligands which can function as inhibitors, or more generally as modifiers of protein function.