1ihx
Crystal structure of two D-glyceraldehyde-3-phosphate dehydrogenase complexes: a case of asymmetry
OverviewOverview
Crystal structures of GAPDH from Palinurus versicolor complexed with two coenzyme analogues, SNAD(+) and ADP-ribose, were determined by molecular replacement and refined at medium resolution to acceptable crystallographic factors and reasonable stereochemistry. ADP-ribose in the ADP-ribose-GAPDH complex adopts a rather extended conformation. The interactions between ADP-ribose and GAPDH are extensive and in a fashion dissimilar to the coenzyme NAD(+). This accounts for the strong inhibiting ability of ADP-ribose. The conformational changes induced by ADP-ribose binding are quite different to those induced by NAD(+) binding. This presumably explains the non-cooperative behaviour of the ADP-ribose binding. Unexpectedly, the SNAD(+)-GAPDH complex reveals pairwise asymmetry. The asymmetry is significant, including the SNAD(+) molecule, active-site structure and domain motion induced by the coenzyme analogue. In the yellow or red subunits [nomenclature of subunits is as in Buehner et al. (1974). J. Mol. Biol. 90, 25-49], SNAD(+) binds similarly, as does NAD(+) in holo-GAPDH. While, in the green or blue subunit, the SNAD(+) binds in a non-productive manner, resulting in a disordered thionicotinamide ring and rearranged active-site residues. The conformation seen in the yellow and red subunits of SNAD(+)-GAPDH is likely to represent the functional state of the enzyme complex in solution and thus accounts for the substrate activity of SNAD(+). A novel type of domain motion is observed for the binding of the coenzyme analogues to GAPDH. The possible conformational transitions involved in the coenzyme binding and the important role of the nicotinamide group are discussed.
About this StructureAbout this Structure
1IHX is a Single protein structure of sequence from Palinurus versicolor. Full crystallographic information is available from OCA.
ReferenceReference
Structures of D-glyceraldehyde-3-phosphate dehydrogenase complexed with coenzyme analogues., Shen YQ, Song SY, Lin ZJ, Acta Crystallogr D Biol Crystallogr. 2002 Aug;58(Pt 8):1287-97. Epub 2002, Jul 20. PMID:12136140 Page seeded by OCA on Fri May 2 20:01:18 2008