Orbital steering in the catalytic power of enzymes: Small structural changes with large catalytic consequences

被引:195
作者
Mesecar, AD
Stoddard, BL
Koshland, DE
机构
[1] LAWRENCE BERKELEY NATL LAB,CTR ADV MAT,BERKELEY,CA
[2] FRED HUTCHINSON CANC RES CTR,PROGRAM STRUCT BIOL,DIV BASIC SCI,SEATTLE,WA 98104
关键词
D O I
10.1126/science.277.5323.202
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Small structural perturbations in the enzyme isocitrate dehydrogenase (IDH) were made in order to evaluate the contribution of precise substrate alignment to the catalytic power of an enzyme. The reaction trajectory of IDH was modified (i) after the adenine moiety of nicotinamide adenine dinucleotide phosphate was changed to hypoxanthine (the 6-amino was changed to 6-hydroxyl), and (ii) by replacing Mg2+, which has six coordinating ligands, with Ca2+, which has eight coordinating ligands. Both changes make large (10(-3) to 10(-5)) changes in the reaction velocity but only small changes in the orientation of the substrates (both distance and angle) as revealed by cryocrystallographic trapping of active IDH complexes. The results provide evidence that orbital overlap produced by optimal orientation of reacting orbitals plays a major quantitative role in the catalytic power of enzymes.
引用
收藏
页码:202 / 206
页数:5
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