Mirroring Perfection: The Structure of Methylglyoxal Synthase Complexed with the Competitive Inhibitor 2-Phosphoglycolate
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- 作者：Dana Saadat and David H. T. Harrison
- 刊名：Biochemistry
- 出版年：2000
- 出版时间：March 21, 2000
- 年：2000
- 卷：39
- 期：11
- 页码：2950 - 2960
- 全文大小：466K
- 年卷期：v.39,no.11(March 21, 2000)
- ISSN：1520-4995
文摘
The crystal structure of the transition-state analogue 2-phosphoglycolate (2PG) bound tomethylglyoxal synthase (MGS) is presented at a resolution of 2.0 Å. This structure is very similar to thepreviously determined structure of MGS complexed to formate and phosphate. Since 2PG is a competitiveinhibitor of both MGS and triosephosphate isomerase (TIM), the carboxylate groups of each bound 2PGfrom this structure and the structure of 2PG bound to TIM were used to align and compare the activesites despite differences in their protein folds. The distances between the functional groups of Asp 71,His 98, His 19, and the carboxylate oxygens of the 2PG molecule in MGS are similar to the correspondingdistances between the functional groups of Glu 165, His 95, Lys 13, and the carboxylate oxygens of the2PG molecule in TIM. However, these spatial relationships are enantiomorphic to each other. Consistentwith the known stereochemical data, the catalytic base Asp 71 is positioned on the opposite face of the2PG-carboxylate plane as Glu 165 of TIM. Both His 98 of MGS and His 95 of TIM are in the plane ofthe carboxylate of 2PG, suggesting that these two residues are homologous in function. While His 19 ofMGS and Lys 13 of TIM appear on the opposite face of the 2PG carboxylate plane, their relative locationto the 2PG molecule is quite different, suggesting that they probably have different functions. Mostremarkably, unlike the coplanar structure found in the 2PG molecule bound to TIM, the torsion anglearound the C1-C2 bond of 2PG bound to MGS brings the phosphoryl moiety out of the molecule'scarboxylate plane, facilitating elimination. Further, the superimposition of this structure with the structureof MGS bound to formate and phosphate suggests a model for the enzyme bound to the first transitionstate.