New insights into the binding mode of coenzymes: Structure of Thermus thermophilus Δ1-pyrroline-5-carboxylate dehydrogenase complexed with NADP+

Eiji Inagaki, Noriyasu Ohshima, Keiko Sakamoto, Nigar D. Babayeva, Hiroaki Kato, Shigeyuki Yokoyama, Tahir H. Tahirov

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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+.

Original languageEnglish (US)
Pages (from-to)462-465
Number of pages4
JournalActa Crystallographica Section F: Structural Biology and Crystallization Communications
Volume63
Issue number6
DOIs
StatePublished - May 5 2007

Keywords

  • Coenzyme binding mode
  • NAD(H)
  • NADP(H)
  • Proline metabolic pathway
  • Δ-pyrroline-5-carboxylate dehydrogenase

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Condensed Matter Physics

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