The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-D-arabinonohydroxamic acid
The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-D-arabinonohydroxamic acid
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DOI：
10.1073/pnas.052131799
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发表时间：
2002-04-30
影响因子：
11.1
通讯作者：
Jeffery, CJ
中科院分区：
文献类型：
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作者：
Arsenieva, D;Hardré, R;Jeffery, CJ
磷酸葡萄糖异构酶（EC 5.3.1.9）催化糖酵解的第二步，即d -葡萄糖6-磷酸可逆异构化为d -果糖6-磷酸。反应机理包括质子转移的酸碱催化，并通过顺式烯二醇（酸）中间体进行。5-磷酸- d -阿拉伯糖羟基肟酸（5PAH）是一种合成的小分子，类似于反应中间体，不同之处在于它用一个氮原子代替了C1。因此，5PAH是迄今为止报道的异构化反应的最佳抑制剂，其K-i为2 × 10(-7) m。本文报道了在1.9埃分辨率下5PAH与兔磷酸葡萄糖异构酶络合的晶体结构。5PAH与酶活性位点氨基酸残基的相互作用支持了一种催化机制模型，其中Glu-357在C1和C2之间转移一个质子，而Arg-272有助于稳定中间体。它还提出了质子在O1和O2之间转移的机制。
Phosphoglucose isomerase (EC 5.3.1.9) catalyzes the second step in glycolysis, the reversible isomerization Of D-glucose 6-phosphate to D-fructose 6-phosphate. The reaction mechanism involves acid-base catalysis with proton transfer and proceeds through a cis-enediol(ate) intermediate. 5-Phospho-D-arabinonohydroxamic acid (5PAH) is a synthetic small molecule that resembles the reaction intermediate, differing only in that it has a nitrogen atom in place of C1. Hence, 5PAH is the best inhibitor of the isomerization reaction reported to date with a K-i of 2 x 10(-7) M. Here we report the crystal structure of rabbit phosphoglucose isomerase complexed with 5PAH at 1.9 Angstrom resolution. The interaction of 5PAH with amino acid residues in the enzyme active site supports a model of the catalytic mechanism in which Glu-357 transfers a proton between C1 and C2 and Arg-272 helps stabilize the intermediate. It also suggests a mechanism for proton transfer between O1 and O2.