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Publication Abstract from PubMed

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(+).

New insights into the binding mode of coenzymes: structure of Thermus thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase complexed with NADP+.,Inagaki E, Ohshima N, Sakamoto K, Babayeva ND, Kato H, Yokoyama S, Tahirov TH Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Jun 1;63(Pt, 6):462-5. Epub 2007 May 5. PMID:17554163^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.