Abstract:
:The enzymic activity of crystalline mitochondrial aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) was determined in suspensions of noncrosslinked microcrystals in 30% (wt/vol) polyethylene glycol. The crystals (average dimensions, 22 x 5 x 0.8 micron) were small enough to preclude diffusional rate limitation. They had the same habit as the triclinic crystals used for the determination of the spatial structure of the enzyme by x-ray crystallographic analysis [Ford, G. C., Eichele, G., and Jansonius, J. N. (1980) Proc. Natl. Acad. Sci. USA 77, 2559-2563]. Determination of the Michaelis-Menten parameters showed that the packing of the enzyme dimer into the crystal lattice not only decreases its activity but also induces a functional nonequivalence of the two subunits that behave identically in solution. The crystalline enzyme possesses a high-affinity subunit with Km values similar to those of the enzyme in solution (K'm = 0.5 mM for aspartate and 1.2 mM for 2-oxoglutarate) and a low-affinity subunit (K'm = 5.5 mM and 14.5 mM, respectively). The catalytic activity of the high-affinity subunit is 3% and that of the low-affinity subunit is 15% of the activity of the enzyme in solution. The functional asymmetry of the crystalline enzyme dimer could also be demonstrated by selective mechanism-based modification of either type of active sites. In view of the apparently identical conformation of the two subunits in the crystalline enzyme, its decreased catalytic efficiency and its functional asymmetry likely are due to constraints exerted by the crystal lattice on the conformational adaptability of the two subunits. In triclinic crystals the two subunits of the enzyme dimer have dissimilar lattice contacts.
journal_name
Proc Natl Acad Sci U S Aauthors
Kirsten H,Gehring H,Christen Pdoi
10.1073/pnas.80.7.1807subject
Has Abstractpub_date
1983-04-01 00:00:00pages
1807-10issue
7eissn
0027-8424issn
1091-6490journal_volume
80pub_type
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