辅酶结合模式的新见解：嗜热栖热菌Δ1-吡咯啉-5-羧酸脱氢酶与NADP+复合物的结构
New insights into the binding mode of coenzymes: structure of Thermus thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase complexed with NADP+.
作者信息
Inagaki Eiji, Ohshima Noriyasu, Sakamoto Keiko, Babayeva Nigar D, Kato Hiroaki, Yokoyama Shigeyuki, Tahirov Tahir H
机构信息
RIKEN SPring-8 Center, Harima Institute, Japan.
出版信息
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Jun 1;63(Pt 6):462-5. doi: 10.1107/S1744309107021422. Epub 2007 May 5.
Delta(1)-Pyrroline-5-carboxylate dehydrogenase (P5CDh) is known to preferentially use NAD(+) as a coenzyme. The k(cat) value of Thermus thermophilus P5CDh (TtP5CDh) is four times lower for NADP(+) than for NAD(+). The crystal structure of NADP(+)-bound TtP5CDh was solved in order to study the structure-activity relationships for the coenzymes. The binding mode of NADP(+) is essentially identical to that in the previously solved NAD(+)-bound form, except for the regions around the additional 2'-phosphate group of NADP(+). The coenzyme-binding site can only accommodate this group by the rotation of a glutamate residue and subtle shifts in the main chain. The 2'-phosphate of NADP(+) increases the number of hydrogen bonds between TtP5CDh and NADP(+) compared with that between TtP5CDh and NAD(+). Furthermore, the phosphate of the bound NADP(+) would restrict the ;bending' of the coenzyme because of steric hindrance. Such bending is important for dissociation of the coenzymes. These results provide a plausible explanation of the lower turnover rate of NADP(+) compared with NAD(+).
已知Δ(1)-吡咯啉-5-羧酸脱氢酶（P5CDh）优先使用NAD⁺作为辅酶。嗜热栖热菌P5CDh（TtP5CDh）对NADP⁺的催化常数（kcat）值比对NAD⁺的低四倍。为了研究辅酶的构效关系，解析了结合NADP⁺的TtP5CDh的晶体结构。除了NADP⁺额外的2'-磷酸基团周围区域外，NADP⁺的结合模式与先前解析的结合NAD⁺形式基本相同。辅酶结合位点只能通过谷氨酸残基的旋转和主链的细微移动来容纳该基团。与TtP5CDh和NAD⁺之间相比，NADP⁺的2'-磷酸增加了TtP5CDh与NADP⁺之间的氢键数量。此外，结合的NADP⁺的磷酸由于空间位阻会限制辅酶的“弯曲”。这种弯曲对于辅酶的解离很重要。这些结果为NADP⁺与NAD⁺相比周转率较低提供了一个合理的解释。
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