New insights into the binding mode of coenzymes: structure of Thermus thermophilusΔ1-pyrroline-5-carboxylate dehydrogenase complexed with NADP+.

Autor: Inagaki, Eiji, Ohshima, Noriyasu, Sakamoto, Keiko, Babayeva, Nigar D., Kato, Hiroaki, Yokoyama, Shigeyuki, Tahirov, Tahir H.
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Zdroj: Acta Crystallographica: Section F (Wiley-Blackwell); Jun2007, Vol. 63 Issue 6, p462-465, 4p, 3 Diagrams, 1 Chart
Abstrakt: Δ1-Pyrroline-5-carboxylate dehydrogenase (P5CDh) is known to preferentially use NAD+ as a coenzyme. The kcat 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+. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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