New insights into the binding mode of coenzymes: structure of Thermus thermophilus Δ1-pyrroline-5-carboxylate dehydrogenase complexed with NADP+
| Autor: | Noriyasu Ohshima, Tahir H. Tahirov, Eiji Inagaki, Shigeyuki Yokoyama, Hiroaki Kato, Nigar D. Babayeva, Keiko Sakamoto |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Stereochemistry
Biophysics Coenzymes Dehydrogenase Crystallography X-Ray Biochemistry Cofactor Bacterial Proteins Structural Biology Oxidoreductase Genetics Glutamate Dehydrogenase (NADP+) Protein Structure Communications chemistry.chemical_classification Binding Sites biology Thermus thermophilus Condensed Matter Physics biology.organism_classification 1-Pyrroline-5-Carboxylate Dehydrogenase Glycerol-3-phosphate dehydrogenase chemistry biology.protein NAD+ kinase NADP |
| Popis: | 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(+). |
| Databáze: | OpenAIRE |
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