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Binding of Coenzyme and Substrate and Coenzyme Analogues to 6-Phosphogluconate Dehydrogenase from Sheep Liver.
- Source :
- European Journal of Biochemistry; 7/16/79, Vol. 98 Issue 1, p121-130, 10p
- Publication Year :
- 1979
-
Abstract
- The analogues of the coenzyme NADP<superscript>+</superscript>, nicotinamide-8-bromo-adenine dinucleotide phosphate (Nbr<superscript>8</superscript>ADP<superscript>+</superscript>) and 3-iodopyridine-adenine dinucleotide phosphate (io<superscript>3</superscript>PdADP<superscript>+</superscript>), were prepared. Nbr<superscript>8</superscript>ADP<superscript>+</superscript> was found to be active in the hydrogen transfer and io<superscript>3</superscript>PdADP<superscript>+</superscript> is a coenzyme competitive inhibitor for 6-phosphogluconate dehydrogenase. The binding of NADP<superscript>+</superscript>, NADPH and NADPH together with 6-phosphogluconate as well as that of both analogues to crystals of the enzyme 6-phosphogluconate dehydrogenase has been investigated at 0.6-nm resolution using difference electron density maps. The molecules bind in a similar position in a cleft in the enzyme subunit distant from the dimer interface. The orientation of the coenzyme in the site has been determined from the io<superscript>3</superscript>pdADP<superscript>+</superscript>-NADP<superscript>+</superscript> difference density. The ternary complex difference density extends beyond that of the nicotinamide moiety of the coenzyme and tentatively indicates substrate binding. No clear identification of the bromine atom of Nbr<superscript>8</superscript>ADP<superscript>+</superscript> can be made. How- ever, the analogue is bound more deeply in the cleft than is NADP<superscript>+</superscript>. The NADPH density is the most clearly defined and has thus been used to fit a molecular model using an interactive graphics system, checking for preferred geometry. A possible conformation is presented which is significantly different from that of NAD<superscript>+</superscript> in the lactate dehydrogenase ternary complex. [ABSTRACT FROM AUTHOR]
- Subjects :
- COENZYMES
LACTATE dehydrogenase
NICOTINAMIDE
ADENINE nucleotides
LIVER
SHEEP
Subjects
Details
- Language :
- English
- ISSN :
- 00142956
- Volume :
- 98
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- European Journal of Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 13679783
- Full Text :
- https://doi.org/10.1111/j.1432-1033.1979.tb13168.x